| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Investigations |
Departments of Urology [G. Y., T. M. W., T. C. T.], Pathology [T. M. W., L. D. T.], Cell Biology [T. C. T.], and Radiology [T. C. T.], Baylor College of Medicine, Houston, Texas 77030
 |
ABSTRACT |
|---|
 Top ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSCorrelation of Caveolin-1...Caveolin-1 as a Predictor...DISCUSSIONREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCorrelation of Caveolin-1...Caveolin-1 as a Predictor...DISCUSSIONREFERENCES |
|---|
We recently developed a strategy to identify mRNAs that are expressed differentially in cell lines derived from primary versus metastatic mouse prostate cancer using differential display PCR. In using this system, a number of metastasis-related sequences were identified including a cDNA that encodes caveolin-1 (9) . Caveolin-1, a Mr 22,000 protein is a major structural component of caveolae, specialized plasma membrane invaginations that are abundant in smooth muscle cells, adipocytes, and endothelium. Caveolae appear to mediate molecular transport, cell adhesion, and signal transduction activities in a cell- and context-specific fashion (10) . Caveolin-1 was found to be overexpressed in both mouse and human metastatic prostate cancer cells (9) . Recently, we documented that suppression of caveolin-1 gene expression with stably transfected antisense caveolin-1 cDNA converted androgen-insensitive metastatic mouse prostate cancer cells to an androgen-sensitive phenotype and that adenovirus-mediated sense caveolin-1 expression blocked androgen sensitivity (11) . Caveolin-1, therefore, has been shown to be a metastasis-related gene as well as a candidate gene for hormone-resistant human prostate cancer. Interestingly, recent studies also point to a potential role for caveolin-1 in the resistance of various malignances to multiple anti-neoplastic agents (12 , 13) .
In the present study, we investigated the possibility of using caveolin-1 expression as a predictive marker for prostate cancer progression. In this retrospective study, 189 clinically confined prostate cancer specimens obtained from radical prostatectomy were immunostained with a caveolin-1-specific antibody. Expression of caveolin-1 was associated with preoperative clinical information of the patients and with postoperative pathological diagnosis. Our results indicate that caveolin-1 expression is a novel independent prognostic marker for progression in clinically confined human prostate cancer.
|
MATERIALS AND METHODS |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCorrelation of Caveolin-1...Caveolin-1 as a Predictor...DISCUSSIONREFERENCES |
|---|
Caveolin-1 Immunohistochemistry.
The sections were deparaffinized and rehydrated. They were then heated in citrate buffer (0.01 M; pH 6.5) with in an 800-Watt microwave oven for 9 min for antigen retrieval. Endogenous peroxidase in sections was inactivated in 2% H2O2 for 10 min. The sections were then blocked in 3% normal goat serum in 0.2 M PBS (pH 7.4), followed by incubation in a rabbit polyclonal antibody to caveolin-1 (Santa Cruz Biotechnology, Santa Cruz, CA). The caveolin-1 antibody was used at a dilution of 1:400 in PBS with 0.5% normal goat serum. The sections were incubated in the primary antibody for 2 h at room temperature. They were then processed following a standard ABC immunostaining procedure with an ABC kit (Vector Lab, Burlingame, CA). Immunoreaction products were visualized in a 3,3'-diaminobenzidine/H2O2 solution. To verify the specificity of the immunoreactions, some sections were incubated in primary antibody preabsorbed by corresponding caveolin-1 peptide (Santa Cruz Biotechnology) at a concentration of 25 µg/ml. The caveolin-1 immunoreactivities were abolished on the sections incubated in the antibody preabsorbed with the caveolin-1 peptide, confirming the specificity of immunostainings.
The immunostained sections were evaluated at a power of x200 under a Zeiss microscope. For each specimen, only the index cancer was evaluated. The entire cancer area was scanned, and an average of 21.76 ± 14.38 (mean ± SD) microscopic fields were evaluated. Positive caveolin-1 staining for a particular specimen was assigned if >50% of the cancer cells in any microscopic field demonstrated caveolin-1-positive granular immunoreaction products in their cytoplasm. All specimens were evaluated without any knowledge of the patients’ clinical information.
Statistical Analysis.
The correlation of caveolin-1 immunoreactivity with patients’ clinical and pathological variables was analyzed by the Spearman or Pearson correlation test. The predictive value of caveolin-1 and other clinical and pathological variables such as preoperative PSA, extraprostatic extension, positive surgical margins, and Gleason score were univariately tested in node-negative patients using a Kaplan-Meier actuarial analysis (17)
and the log-rank test. In addition, multivariate analysis of caveolin-1 immunostaining and the postoperative pathological markers was performed using the Cox proportional hazards regression model (18)
. The risk ratio and its 95% confidence interval were recorded for each marker. P < 0.05 was considered statistically significant in all of the analyses. Moreover, Fisher’s exact test was used to test the differences in the incidence rates of caveolin-1 expression in patients of different pathological and racial subgroups. All analyses were performed with a statistical software (Statview version 5.0; SAS Institute, Inc. Cary, NC).
|
RESULTS |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCorrelation of Caveolin-1...Caveolin-1 as a Predictor...DISCUSSIONREFERENCES |
|---|
, yet the characteristic granular immunoreaction products were present in the cytoplasm of cancer cells (Fig. 1B)
. The caveolin-1-positive cytoplasmic granules varied greatly in their abundance, with a higher density being associated with more poorly differentiated cancer (Fig. 1B)
. In general, caveolin-1 staining within the cancer cell population was heterogeneous, and the proportion of caveolin-1-positive cancer cells varied with individual specimens, ranging from 3.03 to 93.33% and with a median value of 12.50%. According to our criteria (see "Materials and Methods"), 25% of the 189 specimens tested positive for caveolin-1 immunostaining. The incidence of caveolin-1-positive cancers varied with the clinical and pathological variables, as indicated in Table 1
.
|
|
|
Correlation of Caveolin-1 Expression with Clinical and Pathological Variables. |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCorrelation of Caveolin-1...Caveolin-1 as a Predictor...DISCUSSIONREFERENCES |
|---|
. All clinical and pathological parameters, except preoperative PSA and surgical margin status, were correlated with caveolin-1 expression in the complete set of 189 patients. However, because of incomplete data on every patient specimen, the correlation analysis on preoperational PSA levels and on surgical margin was performed only on 128 and 181 patients, respectively (Table 2)
.
|
). Gleason scores for prostatectomy specimens were stratified into well differentiated (Gleason score 3–5; n = 23), moderately differentiated (Gleason score 6–7, n = 143), and poorly differentiated (Gleason score 8–10, n = 23) groups. The caveolin-1-positive cancer rates were 13, 24, and 39% for these groups, respectively. A positive correlation between caveolin-1 and Gleason score was confirmed (correlation coefficient, 0.197; P = 0.0071).
In the caveolin-1-positive specimens for which there was more than one Gleason grade pattern, caveolin-1 expression tended to appear in the poorly differentiated one. To further determine whether there is a correlation between Gleason grade and caveolin-1 expression, a total of 77 cancer foci, which included 5 Gleason grade 2, 49 Gleason grade 3, 20 Gleason grade 4, and 3 Gleason grade 5 patterns, were screened from this set of specimens. The caveolin-1 expression rates were 0, 16, 35, and 33% for Gleason grades 2, 3, 4, and 5 cancers, respectively. A significant correlation between caveolin-1 expression and Gleason grade was found (Spearman correlation test, P = 0.0343).
The caveolin-1-positive cancer rates were significantly higher in the patients who had positive lymph node(s) (41%; n = 27) compared with those with negative nodes (22%; n = 162). A positive correlation between caveolin-1 expression and lymph node metastasis was confirmed (correlation coefficient, 0.150; P = 0.0399, Spearman rank correlation test).
Among the 27 node-positive patients, 21 had metastatic deposits in lymph nodes still available for caveolin-1 immunostaining. A higher caveolin-1-positive cancer rate was found in metastatic tumor deposits (12 of 21; 57%) relative to their primary tumor counterparts (9 of 21; 43%). Of the 21 patients, 8 of 9 who had caveolin-1-positive primary cancer also had caveolin-1-positive lymph node metastases. Subjectively, the proportion of caveolin-1-positive cancer in the metastatic deposits appeared higher than that in their primary counterpart as well.
The frequency of caveolin-1 expression was higher in the cancers with a positive surgical margin (42%; n = 33) compared with those with negative surgical margins (23%; n = 148), and a positive correlation of caveolin-1 with positive surgical margin status was confirmed (correlation coefficient, 0.177; P = 0.0267; Table 2
).
Caveolin-1 expression was somewhat higher in specimens with extraprostatic extension (30%) or seminal vesicle involvement (30%) compared with those without extraprostatic extension (equals level 3 extracapsular extension, Ref. 16
; 20%) or seminal vesicle involvement (24%) correspondingly, but these differences were not statistically significant (Table 2)
. In the 97 patients with extraprostatic extension, 21 also had positive surgical margins, 28 had seminal vesicle involvement, and 2 had both positive margins and seminal vesicle involvement. In the specimens with extraprostatic extension only (n = 46), no significant correlation between caveolin-1 expression and the extraprostatic extension status was found.
In this serial of 189 patients, 166 Caucasian Americans and 11 African Americans were included. The remainder included Hispanic (n = 4), Asian (n = 6), and unknown race (n = 2). The incidence of caveolin-1-positive cancers was higher in African Americans (5 of 11; 45%) than in the Caucasian Americans (42 of 166; 25%), although the difference was not statistically significant in this limited sample set (P = 0.1205, Fisher’s exact test).
|
Caveolin-1 as a Predictor for Time to Disease Progression. |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCorrelation of Caveolin-1...Caveolin-1 as a Predictor...DISCUSSIONREFERENCES |
|---|
When the progression-free probability was plotted versus caveolin-1 staining status, the patients with a caveolin-1-positive cancer had an evident worse prognosis compared with those with caveolin-1-negative cancer (Fig. 2)
. The probabilities of being free of progression after surgery at 60 months were 0.68 ± 0.042 (mean ± SE) for caveolin-1-negative cancer and 0.43 ± 0.08 (mean ± SE) for the caveolin-1-positive cancer.
|
. Age provided no prognostic value in this set of patients.
|
). Gleason score (>7), extraprostatic extension seminal vesicle involvement, as well as positive surgical margins, also had independent prognostic value, with a risk ratio of 4.319 (P = 0.0001), 3.016 (P = 0.004), 2.369 (P = 0.0125), and 1.888 (P = 0.0381), respectively (Table 4)
.
|
|
DISCUSSION |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCorrelation of Caveolin-1...Caveolin-1 as a Predictor...DISCUSSIONREFERENCES |
|---|
60% of newly diagnosed prostate cancers are believed to be organ confined (19)
, yet somewhat <50% of these cancers are found to be confined to prostates, as indicated by final pathological stage after surgical removal of the prostate (5)
. When the cancer is organ confined, progression-free survival is excellent after radical prostatectomy (20)
. In contrast, those that are found not to be confined to the prostate upon pathological analysis are not usually curable by surgery alone and have a much poorer prognosis (8)
. Preoperative PSA levels, clinical stage, and Gleason score have been shown to be useful in predicting clinical outcomes; however, in the middle ranges, these indices lose predictive power. We demonstrated previously that caveolin-1 expression was associated with metastasis in mouse and human prostate cancer (9)
and related to the androgen-resistant phenotype in mouse prostate cancer (11)
. The purpose of the present study was to determine whether caveolin-1 expression of caveolin-1 as determined by immunostaining could provide prognostic value for the patients with clinically confined prostate cancer. In a large set (n = 189) of prostate cancer specimens, 25% were determined to be positive for cancer cell-specific caveolin-1 immunoreactivity. There was a positive correlation of caveolin-1 expression with positive lymph nodes removed at surgery. It was also found that patients with caveolin-1-positive primary cancer tended to have caveolin-1-positive lymph node metastases. These results, together with our previous study that demonstrated a high (56%) incidence of caveolin-1 expression in metastatic deposits within pelvic lymph nodes (9) , indicate a clear association of caveolin-1 expression with development of lymph node metastasis. Once prostate cancer has spread to the regional pelvic lymph nodes, only rarely can it be controlled with any form of local or regional therapy (21) . Virtually all patients with positive nodes treated with surgery alone showed clinical evidence of progression within a 10-year period, and at least 70% of this group will eventually die of cancer rather than with it (22) . The correlation of caveolin-1 expression with positive lymph node metastases, positive surgical margins, as well as Gleason score/grade of the cancer, indicates that caveolin-1 expression is associated with progression/metastasis of prostate cancer. Although the molecular and cellular underpinnings for this relationship are not well understood, our recent study using a mouse prostate cancer model indicated that caveolin-1 levels were higher in metastatic lesions and metastasis-derived cell lines relative to primary tumors and primary tumor-derived cell lines, respectively (9) , and that suppression of caveolin-1 by antisense caveolin-1 vectors converted androgen-resistant metastatic mouse prostate cancer cells to the androgen-sensitive phenotype in vivo (11) . In contrast, adenoviral vector-mediated overexpression of caveolin-1 reestablished androgen resistance in vitro, preventing apoptosis that occurred in control cells after removal of testosterone (11) . These data strongly suggest that elevated caveolin-1 expression promotes survival of prostate cancer cells under conditions that can lead to cell death, including those encountered during metastasis and those generated by androgen withdrawal. Our present results further indicate that caveolin-1 expression in the primary tumor is heterogeneous and highly variable. This pattern of expression is similar to other molecular markers of prostate cancer progression (e.g., p53 mutations) that have been shown to occur at low frequency in the primary tumor but at significantly higher frequency in lymph node metastases (reviewed in Ref. 23 ). Interestingly, both mutations in p53 and overexpression of caveolin-1 have been associated with reduced capacity for apoptosis, supporting the notion that antiapoptotic mutations are important in prostate cancer metastasis. This concept is now further supported by the results from this present study, indicating that caveolin-1 is a positive prognostic marker for a shorter progression-free survival in the clinically localized cancer. Interestingly, two recent reports published shortly after our identification of caveolin-1 overexpression in prostate cancer metastasis (9) and its association with androgen resistance (11) provided strong correlative evidence that caveolin-1 is also associated with the drug resistance phenotype in multiple human carcinoma cell lines (12 , 13) .
In our study, there was also a trend toward higher incidence of caveolin-1-positive cancers in African American patients (45%) compared with Caucasian American patients (25%). The difference, however, was not statistically significant (P = 0.1205; 
2 test), probably because of the relatively small sample size, especially in the black population. It is known that there is a significantly higher rate of prostate cancer incidence and mortality in African Americans compared with Caucasian Americans (24)
, and in general, prostate cancer in African-American men tends to be more aggressive (25)
. Socioeconomic, environmental, as well as biological factors have been attributed to the racial differences (24)
. An obvious question is whether elevated caveolin-1 expression is indeed higher in African-American prostate cancer relative to other ethnic groups and whether this contributes to the more aggressive profile. A larger scale of study with better population control could help to clarify this issue.
In summary, our present study has demonstrated that caveolin-1 expression, as determined by immunohistochemical staining, is associated with positive lymph nodes and positive surgical margins in clinically confined prostate cancers. The possibility of using caveolin-1 expression in needle biopsies as a preoperative marker to predict pathological stage remains to be investigated. However, this potential approach to the use of caveolin-1 immunostaining may be significantly complicated by the multicentric nature of prostate cancer in most patients (26 , 27) , the relatively small and potentially disproportionate quantity of cancer tissue in needle biopsies relative to the cancer volume, and the heterogeneity and likely small proportion of caveolin-1-positive cells in the cancer. On the other hand, the present study clearly revealed that caveolin-1 expression in lymph node-negative human prostate cancer predicts a shorter time to disease progression after radical prostatectomy. Multivariate analysis demonstrated that caveolin-1 expression provides additional prognostic value for disease progression over traditional pathological markers. Thus, evaluation of caveolin-1 expression in surgically removed cancer may facilitate clinical decisions regarding the need for the patients to receive adjuvant treatment postoperatively. The association of caveolin-1 with cancer progression also suggests to us that caveolin-1 itself and possibly specific molecular components involved in its regulation or downstream activities represent targets for the development of novel therapies for metastatic prostate cancer.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
1 This study was supported by Grants CA68814 and Specialized Programs of Research Excellence P50-58204 from the National Cancer Institute. 
2 To whom requests for reprints should be addressed, at Scott Department of Urology, Baylor College of Medicine, 6560 Fannin, Suite 2100, Houston, TX 77030. Phone: (713) 799-8718; Fax: (713) 799-8712; E-mail: timothyt{at}bcm.tmc.edu
3 The abbreviations used are: PSA, prostate-specific antigen; ABC, avidin-biotin complex.
Received 4/14/99. Accepted 9/22/99.
|
REFERENCES |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSCorrelation of Caveolin-1...Caveolin-1 as a Predictor...DISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  A. Gopalan, M. A. Leversha, J. M. Satagopan, Q. Zhou, H. A. Al-Ahmadie, S. W. Fine, J. A. Eastham, P. T. Scardino, H. I. Scher, S. K. Tickoo, et al. TMPRSS2-ERG Gene Fusion Is Not Associated with Outcome in Patients Treated by Prostatectomy Cancer Res., February 15, 2009; 69(4): 1400 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Palozza, R. Sestito, N. Picci, P. Lanza, G. Monego, and F. O. Ranelletti The sensitivity to {beta}-carotene growth-inhibitory and proapoptotic effects is regulated by caveolin-1 expression in human colon and prostate cancer cells Carcinogenesis, November 1, 2008; 29(11): 2153 - 2161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Joshi, S. S. Strugnell, J. G. Goetz, L. D. Kojic, M. E. Cox, O. L. Griffith, S. K. Chan, S. J. Jones, S.-P. Leung, H. Masoudi, et al. Phosphorylated Caveolin-1 Regulates Rho/ROCK-Dependent Focal Adhesion Dynamics and Tumor Cell Migration and Invasion Cancer Res., October 15, 2008; 68(20): 8210 - 8220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Tan and M. T Nevalainen Signal transducer and activator of transcription 5A/B in prostate and breast cancers Endocr. Relat. Cancer, June 1, 2008; 15(2): 367 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Goetz, B. Joshi, P. Lajoie, S. S. Strugnell, T. Scudamore, L. D. Kojic, and I. R. Nabi Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1 J. Cell Biol., March 24, 2008; 180(6): 1261 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Arnold, J. He, A. Remo, D. Ritsick, Q. Yin-Goen, J. D. Lambeth, M. W. Datta, A. N. Young, and J. A. Petros Nox1 Expression Determines Cellular Reactive Oxygen and Modulates c-fos-Induced Growth Factor, Interleukin-8, and Cav-1 Am. J. Pathol., December 1, 2007; 171(6): 2021 - 2032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, M.-T. Ling, Q. Wang, C.-K. Lau, S. C. L. Leung, T. K. Lee, A. L. M. Cheung, Y.-C. Wong, and X. Wang Identification of a Novel Inhibitor of Differentiation-1 (ID-1) Binding Partner, Caveolin-1, and Its Role in Epithelial-Mesenchymal Transition and Resistance to Apoptosis in Prostate Cancer Cells J. Biol. Chem., November 16, 2007; 282(46): 33284 - 33294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Torres, J. C. Tapia, D. A. Rodriguez, A. Lladser, C. Arredondo, L. Leyton, and A. F. G. Quest E-Cadherin Is Required for Caveolin-1-Mediated Down-Regulation of the Inhibitor of Apoptosis Protein Survivin via Reduced {beta}-Catenin-Tcf/Lef-Dependent Transcription Mol. Cell. Biol., November 1, 2007; 27(21): 7703 - 7717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lajoie, E. A. Partridge, G. Guay, J. G. Goetz, J. Pawling, A. Lagana, B. Joshi, J. W. Dennis, and I. R. Nabi Plasma membrane domain organization regulates EGFR signaling in tumor cells J. Cell Biol., October 22, 2007; 179(2): 341 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Siddiqui, K. A. Harvey, G. P. Zaloga, and W. Stillwell Modulation of Lipid Rafts by {Omega}-3 Fatty Acids in Inflammation and Cancer: Implications for Use of Lipids During Nutrition Support Nutr Clin Pract, February 1, 2007; 22(1): 74 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Tahir, A. Frolov, T. G. Hayes, M. P. Mims, B. J. Miles, S. P. Lerner, T. M. Wheeler, G. Ayala, T. C. Thompson, and D. Kadmon Preoperative Serum Caveolin-1 as a Prognostic Marker for Recurrence in a Radical Prostatectomy Cohort. Clin. Cancer Res., August 15, 2006; 12(16): 4872 - 4875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Ayala, H. Dai, S. A. Tahir, R. Li, T. Timme, M. Ittmann, A. Frolov, T. M. Wheeler, D. Rowley, and T. C. Thompson Stromal antiapoptotic paracrine loop in perineural invasion of prostatic carcinoma. Cancer Res., May 15, 2006; 66(10): 5159 - 5164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Schwencke, R. C. Braun-Dullaeus, C. Wunderlich, and R. H. Strasser Caveolae and caveolin in transmembrane signaling: Implications for human disease Cardiovasc Res, April 1, 2006; 70(1): 42 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Hughes, A Murphy, C Martin, O Sheils, and J O'Leary Molecular pathology of prostate cancer J. Clin. Pathol., July 1, 2005; 58(7): 673 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Williams, G. S. Hassan, J. Li, A. W. Cohen, F. Medina, P. G. Frank, R. G. Pestell, D. Di Vizio, M. Loda, and M. P. Lisanti Caveolin-1 Promotes Tumor Progression in an Autochthonous Mouse Model of Prostate Cancer: GENETIC ABLATION OF Cav-1 DELAYS ADVANCED PROSTATE TUMOR DEVELOPMENT IN TRAMP MICE J. Biol. Chem., July 1, 2005; 280(26): 25134 - 25145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Cavallo-Medved, J. Mai, J. Dosescu, M. Sameni, and B. F. Sloane Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells J. Cell Sci., April 1, 2005; 118(7): 1493 - 1503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Williams and M. P. Lisanti Caveolin-1 in oncogenic transformation, cancer, and metastasis Am J Physiol Cell Physiol, March 1, 2005; 288(3): C494 - C506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Williams, F. Medina, I. Badano, R. B. Hazan, J. Hutchinson, W. J. Muller, N. G. Chopra, P. E. Scherer, R. G. Pestell, and M. P. Lisanti Caveolin-1 Gene Disruption Promotes Mammary Tumorigenesis and Dramatically Enhances Lung Metastasis in Vivo: ROLE OF CAV-1 IN CELL INVASIVENESS AND MATRIX METALLOPROTEINASE (MMP-2/9) SECRETION J. Biol. Chem., December 3, 2004; 279(49): 51630 - 51646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Llorente, M. C. de Marco, and M. A. Alonso Caveolin-1 and MAL are located on prostasomes secreted by the prostate cancer PC-3 cell line J. Cell Sci., October 15, 2004; 117(22): 5343 - 5351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Aldred, Y. Huang, S. Liyanarachchi, N. S. Pellegata, O. Gimm, S. Jhiang, R. V. Davuluri, A. de La Chapelle, and C. Eng Papillary and Follicular Thyroid Carcinomas Show Distinctly Different Microarray Expression Profiles and Can Be Distinguished by a Minimum of Five Genes J. Clin. Oncol., September 1, 2004; 22(17): 3531 - 3539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kim, R. M. Adam, K. R. Solomon, and M. R. Freeman Involvement of Cholesterol-Rich Lipid Rafts in Interleukin-6-Induced Neuroendocrine Differentiation of LNCaP Prostate Cancer Cells Endocrinology, February 1, 2004; 145(2): 613 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, C. H. Ren, S. A. Tahir, C. Ren, and T. C. Thompson Caveolin-1 Maintains Activated Akt in Prostate Cancer Cells through Scaffolding Domain Binding Site Interactions with and Inhibition of Serine/Threonine Protein Phosphatases PP1 and PP2A Mol. Cell. Biol., December 15, 2003; 23(24): 9389 - 9404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Carver, J. E. Schnitzer, R. G. W. Anderson, and S. Mohla Role of Caveolae and Lipid Rafts in Cancer: Workshop Summary and Future Needs Cancer Res., October 15, 2003; 63(20): 6571 - 6574. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Tahir, C. Ren, T. L. Timme, Y. Gdor, R. Hoogeveen, J. D. Morrisett, A. Frolov, G. Ayala, T. M. Wheeler, and T. C. Thompson Development of an Immunoassay for Serum Caveolin-1: A Novel Biomarker for Prostate Cancer Clin. Cancer Res., September 1, 2003; 9(10): 3653 - 3659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Aldred, M. E. Ginn-Pease, C. D. Morrison, A. P. Popkie, O. Gimm, C. Hoang-Vu, U. Krause, H. Dralle, S. M. Jhiang, C. Plass, et al. Caveolin-1 and Caveolin-2,Together with Three Bone Morphogenetic Protein-related Genes, May Encode Novel Tumor Suppressors Down-Regulated in Sporadic Follicular Thyroid Carcinogenesis Cancer Res., June 1, 2003; 63(11): 2864 - 2871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Cao, G. Yang, T. L. Timme, T. Saika, L. D. Truong, T. Satoh, A. Goltsov, S. H. Park, T. Men, N. Kusaka, et al. Disruption of the Caveolin-1 Gene Impairs Renal Calcium Reabsorption and Leads to Hypercalciuria and Urolithiasis Am. J. Pathol., April 1, 2003; 162(4): 1241 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-C. Ho, P.-H. Huang, H.-Y. Huang, Y.-H. Chen, P.-C. Yang, and S.-M. Hsu Up-Regulated Caveolin-1 Accentuates the Metastasis Capability of Lung Adenocarcinoma by Inducing Filopodia Formation Am. J. Pathol., November 1, 2002; 161(5): 1647 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wu and D. M. Terrian Regulation of Caveolin-1 Expression and Secretion by a Protein Kinase Cepsilon Signaling Pathway in Human Prostate Cancer Cells J. Biol. Chem., October 18, 2002; 277(43): 40449 - 40455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhuang, J. Lin, M. L. Lu, K. R. Solomon, and M. R. Freeman Cholesterol-rich Lipid Rafts Mediate Akt-regulated Survival in Prostate Cancer Cells Cancer Res., April 1, 2002; 62(8): 2227 - 2231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wu, T. L. Foreman, C. W. Gregory, M. A. McJilton, G. G. Wescott, O. H. Ford, R. F. Alvey, J. L. Mohler, and D. M. Terrian Protein Kinase C{epsilon} Has the Potential to Advance the Recurrence of Human Prostate Cancer Cancer Res., April 1, 2002; 62(8): 2423 - 2429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pramudji, S. Shimura, S. Ebara, G. Yang, J. Wang, C. Ren, Y. Yuan, S. A. Tahir, T. L. Timme, and T. C. Thompson In Situ Prostate Cancer Gene Therapy Using a Novel Adenoviral Vector Regulated by the Caveolin-1 Promoter Clin. Cancer Res., December 1, 2001; 7(12): 4272 - 4279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Wolfgang, M. Essand, B. Lee, and I. Pastan T-Cell Receptor {gamma} Chain Alternate Reading Frame Protein (TARP) Expression in Prostate Cancer Cells Leads to an Increased Growth Rate and Induction of Caveolins and Amphiregulin Cancer Res., November 1, 2001; 61(22): 8122 - 8126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Wiechen, L. Diatchenko, A. Agoulnik, K. M. Scharff, H. Schober, K. Arlt, B. Zhumabayeva, P. D. Siebert, M. Dietel, R. Schafer, et al. Caveolin-1 Is Down-Regulated in Human Ovarian Carcinoma and Acts as a Candidate Tumor Suppressor Gene Am. J. Pathol., November 1, 2001; 159(5): 1635 - 1643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsuyama, Y. Pan, K. Oba, S. Yoshihiro, K. Matsuda, L. Hagarth, D. Kudren, K. Naito, U. S. R. Bergerheim, and P. Ekman Deletions on Chromosome 8p22 May Predict Disease Progression As Well As Pathological Staging in Prostate Cancer Clin. Cancer Res., October 1, 2001; 7(10): 3139 - 3143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, G. Yang, S. Ebara, T. Satoh, Y. Nasu, T. L. Timme, C. Ren, J. Wang, S. A. Tahir, and T. C. Thompson Caveolin-1 Mediates Testosterone-stimulated Survival/Clonal Growth and Promotes Metastatic Activities in Prostate Cancer Cells Cancer Res., June 1, 2001; 61(11): 4386 - 4392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Tahir, G. Yang, S. Ebara, T. L. Timme, T. Satoh, L. Li, A. Goltsov, M. Ittmann, J. D. Morrisett, and T. C. Thompson Secreted Caveolin-1 Stimulates Cell Survival/Clonal Growth and Contributes to Metastasis in Androgen-insensitive Prostate Cancer Cancer Res., May 1, 2001; 61(10): 3882 - 3885. [Abstract] [Full Text]
|
|
|
|
|
|
K. Wiechen, C. Sers, A. Agoulnik, K. Arlt, M. Dietel, P. M. Schlag, and U. Schneider Down-Regulation of Caveolin-1, a Candidate Tumor Suppressor Gene, in Sarcomas Am. J. Pathol., March 1, 2001; 158(3): 833 - 839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Ozanne, M. E. Brady, S. Cook, L. Gaughan, D. E. Neal, and C. N. Robson Androgen Receptor Nuclear Translocation Is Facilitated by the f-Actin Cross-Linking Protein Filamin Mol. Endocrinol., October 1, 2000; 14(10): 1618 - 1626. [Abstract] [Full Text]
|
|
|
|
|
|
G. Yang, J. Addai, M. Ittmann, T. M. Wheeler, and T. C. Thompson Elevated Caveolin-1 Levels in African-American versus White-American Prostate Cancer Clin. Cancer Res., September 1, 2000; 6(9): 3430 - 3433. [Abstract] [Full Text]
|
|
|
|
|
|
M. L. Lu, M. C. Schneider, Y. Zheng, X. Zhang, and J. P. Richie Caveolin-1 Interacts with Androgen Receptor. A POSITIVE MODULATOR OF ANDROGEN RECEPTOR MEDIATED TRANSACTIVATION J. Biol. Chem., April 13, 2001; 276(16): 13442 - 13451. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
