Cancer Research Cancer Health Disparities Conference 2009 SU2C
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
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kim, I. Y.
Right arrow Articles by Morton, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, I. Y.
Right arrow Articles by Morton, R. A.
[Cancer Research 60, 2840-2844, June 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Expression of Bone Morphogenetic Protein Receptors Type-IA, -IB, and -II Correlates with Tumor Grade in Human Prostate Cancer Tissues1

Isaac Yi Kim, Dong-Hyeon Lee, Han-Jong Ahn, Hideo Tokunaga, Weitao Song, Lisa M. Devereaux, Donald Jin, T. Kuber Sampath and Ronald A. Morton2

Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030 [I. Y. K., D-H. L., H. T., W. S., L. M. D., R. A. M.]; Department of Urology, University of Ulsan, Seoul, Korea [H-J. A.]; and Creative Biomolecules, Hopkinton, Massachusetts 01748 [D. J., T. K. S.]


   ABSTRACT
Top
 ABSTRACT
Introduction
 Materials and Methods
 Results
 Discussion
 REFERENCES
 
Bone morphogenetic proteins (BMPs) are potential regulators of prostate cancer cell growth and metastasis that signal through an interaction with BMP membrane receptors (BMPRs) type I and type II. In the present study, Western blot and immunohistochemical analysis of BMPRs were carried out in benign and malignant human prostate tissues to explain the loss of BMP response in human prostate cancer cells. The results demonstrated that the benign prostate specimens expressed high levels of all three BMPRs. In normal prostate, BMPRs were localized predominantly to epithelial cells. Among prostate cancer specimens, well-differentiated cancers were positive for the expression of BMPR-II, BMPR-IA, and BMPR-IB, for the most part. In contrast, only 1 of 10 poorly differentiated prostate cancer cases was positive for each of the three BMPRs (P < 0.005 for all three receptors). Taken together, these results indicate that human prostate cancer cells frequently exhibit loss of expression of BMPRs and suggest that loss of BMPRs may play an important role during the progression of prostate cancer.


   Introduction
Top
 ABSTRACT
 Introduction
Materials and Methods
 Results
 Discussion
 REFERENCES
 
Prostate cancer is the most common malignancy and the second leading cause of male cancer deaths in the United States (1) . At the present time, the precise mechanism involved in prostate carcinogenesis remains uncertain. Nevertheless, it is likely that there are certain genetic alterations in prostatic epithelial cells that permit them to proliferate and metastasize. In this regard, it has been suggested that BMPs3 play a role during prostate carcinogenesis (2 , 3) . BMPs, the largest subgroup within the TGF-ß superfamily, were originally isolated as factors that induce bone and cartilage formation (4, 5, 6) . Recent work has demonstrated that normal BMP function is critical during mammalian development, cellular chemotaxis, and cellular differentiation (7, 8, 9) . Based on sequence homology, BMPs are divided into three subgroups: (a) BMP-2 and -4; (b) BMP-5, -6, -7, and -8; and (c) BMP-3 (10) . Investigation of BMP knockout mice suggests that each type of BMP may function independently (11 , 12) . However, the specific role(s) for each type of BMP remains unclear. BMP signal transduction follows the paradigm established by TGF-ß signaling. As with TGF-ß, BMPs signal through an interaction with a heteromeric complex of BMPRs, BMPR-I and -II. Specifically, ligand binding results in cross-phosphorylation of BMPR-I by BMPR-II; BMPR-I, in turn, propagates BMP signaling (13) . In vitro experiments have shown that all members of BMP that belong to the TGF-ß superfamily bind to BMPR-II in combination with BMPR-IA or -IB (14 , 15) . In contrast, BMP-4 does not bind to ActR-II or ActR-I (13) . Thus, it has been suggested that BMPR-IA, -IB, and -II are BMP-specific receptors. In prostate cancer, it has been shown that BMP-2 decreases the rate of proliferation of LNCaP but not of TSU-PR1, PC3, and DU145 cells (16) . Because these three prostate cancer cell lines are insensitive to the growth-inhibitory effect of BMP-2, it is possible that some primary human prostate cancer cells are also insensitive to BMPs. The exact mechanism for rendering insensitivity to BMPs has not been established. As an initial attempt to investigate the mechanism underlying the loss of sensitivity to BMPs, we have determined the expression of BMP-specific receptors (BMPR-II, -IA, and -IB) in archival human prostate cancer specimens. We report that the expression of BMPRs is frequently lost in high-grade prostate cancer cells.


   Materials and Methods
Top
 ABSTRACT
 Introduction
 Materials and Methods
Results
 Discussion
 REFERENCES
 
Tissue Specimens.
Fomalin-fixed and paraffin-embedded tissue specimens of 40 histopathologically diagnosed prostate cancer samples and 10 samples of benign prostate were obtained from the archives of the Scott Department of Urology, Baylor College of Medicine (Houston, TX) and the Department of Urology, University of Ulsan (Seoul, Korea). Tumor specimens were divided into 10 cases of well-differentiated cancer, 20 cases of moderately differentiated cancer, and 10 cases of poorly differentiated cancer, according to the Gleason score (17) . Sections were cut at 4.0 µm and kept at room temperature until use. The first and last section from each specimen was stained with H&E to verify histopathological diagnosis.

Immunohistochemistry.
Anti-BMPR antibodies were kindly provided by Dr. Kohei Miyazono of The Cancer Institute (Tokyo, Japan). The specificity of the antibodies has been established previously (18 , 19) .

Archival specimens fixed in neutral buffered formalin were sectioned at a thickness of 4 µm, deparaffinized in Xylene (Fisher Scientific Co., Pittsburgh, PA), and rehydrated in PBS. Endogenous peroxidase activity was inactivated by incubation in 0.3% H2O2 for 10 min. After a preincubation with 2% normal goat serum to block nonspecific sites, the sections were incubated with primary antibodies in a humidified chamber for 18 h at 4°C. Anti-BMPR-IA, anti-BMPR-IB, and anti-BMPR-II antibodies were used at a concentration of 4 µg/ml. Antigenic binding sites were visualized with a serial incubation with biotinylated secondary antibody, followed by avidin-biotin-horseradish peroxidase complex and diaminobenzidine tetrahydrochloride before counterstaining with Gill’s hematoxylin (ABC kit; Vector Laboratories, Burlingame, CA). Negative control sections were processed in an identical manner by substitution of primary antibody with a normal rabbit IgG fraction. All negative control sections showed no color reaction.

All cases were classified into groups that showed either positive or negative staining for BMPRs. Specimens were classified as positive if >10% of cells had a staining intensity greater than that of negative control slides per high-power field. At the least three high-power fields were reviewed for each case. All cases were confirmed with at least two independent staining experiments. In addition, all staining specimens were reviewed by two blinded independent investigators.

Western Blot Analysis.
Frozen normal and malignant prostate tissues were homogenized with PBS at 4°C, and the protein concentration was determined. Samples were placed in sample buffer (0.0625 M Trizma base, 2% SDS, and 5% 2-mercaptoethanol) and boiled for 5 min. Electrophoresis was carried out in a 10% SDS-polyacrylamide gel using 100 µg of total protein in each lane. After electrophoresis, proteins were transferred to a 0.2-µm nitrocellulose membrane (Bio-Rad). After the transfer, the membranes were incubated overnight in blocking buffer (5% nonfat dry milk, PBS, and 0.1% Tween). Subsequently, the membranes were incubated with appropriate antibodies at a dilution of 1:400 overnight at 4°C. After washing with PBS-0.1% Tween, the membranes were incubated in the presence of goat antirabbit horseradish peroxidase-labeled secondary antibody (Bio-Rad) at a dilution of 1:3000 for 2 h at room temperature. After washing several times, immunoreactive bands were visualized by enhanced chemiluminescence (Amersham).

Statistics.
The correlation between BMPR expression and tumor grade was evaluated by the {chi}2 test. P < 0.05 was considered statistically significant.


   Results
Top
 ABSTRACT
 Introduction
 Materials and Methods
 Results
Discussion
 REFERENCES
 
Expression of BMPRs in Benign Prostate Tissues.
Initially, the expression of BMPRs was investigated in benign human prostate tissues by immunohistochemistry. In benign tissues, the expression of BMPR-IA, -IB, and -II was predominantly localized in the epithelial cells (Fig. 1Citation ). As described previously (18 , 19) , the specificity of the antibodies was confirmed by successfully neutralizing the color reactions when the antibodies were preincubated with 100-fold molar excess of the corresponding peptide antigen (data not shown).



View larger version (87K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 1. Immunohistochemistry for BMPRs in benign human prostate tissues. Note the dark positively stained cells. All three receptors were expressed predominantly by epithelial cells.

 
Expression of BMPRs in Malignant Prostate Tissues.
To determine whether or not a significant portion of human prostate cancer cases have reduced levels of BMPRs, 40 archival samples were screened for BMPR expression using immunohistochemistry (Table 1)Citation . For comparison, 10 samples of benign prostatic tissues were used. Fig. 2Citation ,A–C, shows representative immunohistochemical staining for BMPR-IA, -IB, and -II, respectively. There was a wide variation in staining intensity for BMPR expression among the human prostate cancer specimens. The tissue samples were classified into groups that showed either positive or negative staining for BMPR expression. No attempt was made to quantitate the levels of expression of BMPRs among positively stained specimens. All benign prostate tissues were positive for expression of all three BMPR proteins. However, with increasing tumor grade, prostate cancers demonstrated a progressive loss of BMPR protein expression. Table 2Citation shows the relationship between the loss of expression of BMPRs and grade of prostate malignancy by dividing the cancer tissue specimens into three classes, based on the Gleason score (16) : (a) 10 well-differentiated cancers (Gleason score, 2–4); (b) 20 moderately differentiated cancers (Gleason score, 5–7); and (c) 10 poorly differentiated cancers (Gleason score 8–10). In 10 of 10 benign prostate samples, all three BMPRs were readily detected. Similarly, seven, eight, and nine samples of well-differentiated cancers expressed BMPR-II, BMPR-IA, and BMPR-IB, respectively. In contrast, only 1 of 10 samples of poorly differentiated cancers expressed detectable levels of the three BMPRs investigated in this study. The frequency of loss of expression of BMPRs in prostate cancer cells was statistically significant in each group (P < 0.005 for all three BMPRs).


View this table:
[in this window]
[in a new window]

  		Table 1 Expression of BMPRs in human prostate cancer tissues

 


View larger version (95K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 2. Immunohistochemistry for BMPRs in malignant human prostate tissues. A, BMPR-IA; B, BMPR-IB; C, BMPR-II. There was a significant decrease in the level of expression of all three receptors in prostate cancer tissues.

 

View this table:
[in this window]
[in a new window]

  		Table 2 Relationship of BMPR expression to tumor grade

 
To further demonstrate that prostate cancer tissues have decreased levels of BMPR expression, Western blot analysis was carried out. As shown in Fig. 3Citation , normal prostate tissues had readily detectable levels of the three BMPRs (Lanes 1 and 2). On the other hand, prostate cancer tissues frequently showed loss of BMPR expression (Lanes 3–7). Specifically, three of five prostate cancer tissues examined had decreased levels of BMPR-II expression. With regard to type I receptors, three of five and five of five malignant prostate tissues had decreased levels of expression of BMPR-IA and BMPR-IB, respectively.



View larger version (44K):
[in this window]
[in a new window]
[Download PPT slide]
  		Fig. 3. Western blot analysis for BMPRs in normal and prostate cancer tissues. Lanes 1 and 2, normal prostate; Lanes 3–7, prostate cancer. Three of the five prostate cancer tissues show decreased levels of BMPR-II expression. With regard to type I BMPRs, three of five and five of five prostate cancer specimens show decreased levels of expression of BMPR-IA and -IB, respectively.

 

   Discussion
Top
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
REFERENCES
 
These data demonstrate that BMPRs are preferentially expressed by epithelial cells in the human prostate and that human prostate cancer cells frequently have reduced levels of expression of BMPR-IA, BMPR-IB, and BMPR-II. The results also show an inverse correlation between the levels of BMPR expression and tumor grade in human prostate malignancy. Taken together, these observations provide a valuable insight regarding the potential role of BMPs during carcinogenesis in the human prostate.

It has been suggested that members of TGF-ß superfamily mediate stromal-epithelial cell interaction in the normal prostate. Specifically, TGF-ß is predominantly expressed by prostate stromal cells, whereas TGF-ß receptors are present in high concentrations among prostate epithelial cells (20 , 21) . In the present study, the expression of BMPRs was localized mainly to the epithelial compartment. Such preferential expression of BMPRs by the prostatic epithelial cells also suggests that BMPs may be a mediator of stromal-epithelial interaction. Further work is necessary to verify this hypothesis.

The accepted mechanism of carcinogenesis is a process involving multiple molecular genetic alterations. To date, the exact molecular mechanism of prostate carcinogenesis is incompletely understood. Nevertheless, the development and progression of prostate cancer likely involve multiple steps and factors. In this regard, the results of the present study suggest that loss of BMPRs may play a role during prostate carcinogenesis. Of the 40 prostate cancer cases investigated in this study, 32 (80%) exhibited loss of expression of one or more BMPR. Of the 32 cases, 25 had either loss of BMPR-II or loss of BMPR-I (BMPR-IA or BMPR-IB). Since BMP signaling requires both type I and type II receptors for BMP signaling, 25 of 40 cases (62%) investigated in the present study likely had defective BMP signaling. Recently, it has been demonstrated that BMP-2 inhibits the proliferation of a prostate cancer cell line, LNCaP (16) . Taken together, these observations suggest that BMPs are growth-inhibitory factors and that some prostate cancer cells acquire resistance to the growthinhibitory effect of BMPs through down-regulation of receptor expression.

The frequent loss of BMPRs in high-grade prostate cancer cells also suggests a potential mechanism for the high frequency of metastasis to bone in prostate cancer patients. Because the normal bone has relatively high concentrations of BMPs, which normally inhibit cellular proliferation (22) , prostate cancer cells that retain BMP signaling will not be able to proliferate in such a microenvironment. On the other hand, prostate cancer cells that have a loss of BMPRs are released from the growth-inhibitory effect of BMPs and will be able to proliferate in the bone. Further analysis is necessary to confirm this hypothesis.

Finally, the results of the present study suggest that the loss of BMPRs may be used as a prognostic marker in prostate cancer patients. Specifically, there was an inverse correlation between the loss of BMPR expression and increasing tumor grade (Gleason score) because 10 of 10 poorly differentiated prostate cancer cases had a loss of one of the three BMPRs; on the other hand, only 5 of 10 well-differentiated prostate cancer cases had loss of expression of one of these receptors. Because Gleason score is one of the best available predictors of outcome among prostate cancer patients, an association between Gleason score and the loss of BMPR expression suggests that the status of BMPRs may also be used as a prognostic marker in prostate cancer patients. Currently, the possibility that the status of BMPR expression functions as an independent prognostic marker in prostate cancer patients is under investigation.

In conclusion, the results of the present study have demonstrated that human prostate epithelial cells preferentially express BMPR-IA, BMPR-IB, and BMPR-II and that prostate cancer cells frequently have loss of expression of these receptors. In the future, the specific roles and expression of each BMPR during the progression and metastasis of prostate cancer will be the subject of investigation.


   FOOTNOTES
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported in part by USPHS Grant 58204. Back

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) 798-4653; Fax: (713) 798-8030. Back

3 The abbreviations used are: BMP, bone morphogenetic protein; BMPR, BMP membrane receptor; TGF, transforming growth factor. Back

Received 9/14/99. Accepted 4/14/00.


   REFERENCES
Top
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
 REFERENCES
 

  1. Landis S. H., Murray T., Bolden S., Wingo P. A. Cancer statistics, 1999. CA Cancer J. Clin., 49: 8-31, 1999.[Abstract/Free Full Text]
  2. Ide H., Katoh M., Sasaki H., Yoshida T., Aoki K., Nawa Y., Osada Y., Sugimura T., Terada M. Cloning of human bone morphogenetic protein type IB receptor (BMPR-IB) and its expression in prostate cancer in comparison with other BMPRs. Oncogene, 14: 1377-1382, 1997.[Medline]
  3. Autzen P., Robson C. N., Bjartell A., Malcolm A. J., Johnson M. I., Neal D. E., Hamdy F. C. Bone morphogenetic protein 6 in skeletal metastases from prostate cancer and other common human malignancies. Br. J. Cancer, 78: 1219-1223, 1998.[Medline]
  4. Wozney J. M., Rosen V., Celeste A. J., Mitsock L. M., Whitters M. J., Kriz R. W., Hewick R. M., Wang E. A. Novel regulators of bone formation: molecular clones and activities. Science (Washington DC), 242: 1528-1534, 1988.[Abstract/Free Full Text]
  5. Wozney J. M. The bone morphogenetic protein family and osteogenesis. Mol. Reprod. Dev., 32: 160-167, 1992.[Medline]
  6. Sampath T. K., Maliakal J. C., Hauschka P. V., Jones W. K., Sasak H., Tucker R. F., White K. H., Coughlin J. E., Tucker M. M., Pang R. H. L. Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteblast proliferation and differentiation in vitro.. J. Biol. Chem., 267: 20352-20362, 1992.[Abstract/Free Full Text]
  7. Hogan B. L. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev., 10: 1580-1594, 1996.[Free Full Text]
  8. Lind M., Eriksen E. F., Bunger C. Bone morphogenetic protein-2 but not bone morphogenetic protein-4 and -6 stimulates chemotactic migration of human osteoblasts, human marrow osteoblasts, and U2-OS cells. Bone, 18: 53-57, 1996.[Medline]
  9. Paralkar V. M., Weeks B. S., Yu Y. M., Kleinman H. K., Reddi A. H. Recombinant human bone morphogenetic protein 2B stimulates PC12 cell differentiation: potentiation and binding to type IV collagen. J. Cell. Biol., 119: 1721-1728, 1992.[Abstract/Free Full Text]
  10. Massague J., Weis-Garcia F. Serine/threonine kinase receptors: mediators of transforming growth factor ß family signals. Cancer Surv., 27: 41-64, 1996.[Medline]
  11. Winnier G., Blessing M., Labosky P. A., Hogan B. L. M. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev., 9: 2105-2116, 1995.[Abstract/Free Full Text]
  12. Luo G., Hofman C., Bronckers A. L. J. J., Sohocki M., Bradley A., Karsentry G. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev., 9: 2808-2820, 1995.[Abstract/Free Full Text]
  13. Yamashita H., Ten-Dijke P., Heldin C-H., Miyazono K. Bone morphogenetic protein receptors. Bone, 19: 569-574, 1996.[Medline]
  14. Liu F., Ventura F., Doody J., Massague J. Human type II receptor for bone morphogenetic proteins (BMPs): extension of the two-kinase receptor model to BMPs. Mol. Cell. Biol., 15: 3479-3486, 1995.[Abstract]
  15. ten Dijke P., Yamashita H., Sampath T. K., Reddi A. H., Esterez M., Riddle D. L., Ichijo H., Heldin C. H., Miyazono K. Introduction of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. J. Biol. Chem., 269: 16985-16988, 1994.[Abstract/Free Full Text]
  16. Ide H., Yoshida T., Matsumoto N., Aoki K., Osada Y., Sugimura T., Terada M. Growth regulation of human prostate cancer cells by bone morphogenetic protein-2. Cancer Res., 57: 5022-5027, 1997.[Abstract/Free Full Text]
  17. Gleason P. F., Mellinger G., the Veterans Administeration Cooperative Urological Research Group. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J. Urol., 111: 58-64, 1974.[Medline]
  18. Yonemori K., Imamura T., Ishidou Y., Okano T., Matsunaga S., Yoshida H., Kato M., Sampath T. K., Miyazono K., Ten Dijke P., Sakou T. Bone morphogenetic protein receptors and activin receptors are highly expressed in ossified ligament tissues of patients with ossification of the posterior longitudinal ligament. Am. J. Pathol., 150: 1335-1347, 1997.[Abstract]
  19. Yamada N., Kato M., Ten Dijke P., Yamashita H., Sampath T. K., Heldin C-H., Miyazono K., Funa K. Bone morphogenetic protein type IB receptor is progressively expressed in malignant glioma tumors. Br. J. Cancer, 73: 624-629, 1996.[Medline]
  20. Nemeth J. A., Sensibar J. A., White R. R., Zelner D. J., Kim I. Y., Lee C. The prostatic ductal system in rats: tissue-specific expression and regional variation in stromal distribution of transforming growth factor-ß1. Prostate, 33: 64-71, 1997.[Medline]
  21. Kim I. Y., Ahn H-J., Zelner D. J., Park L., Sensibar J. A., Lee C. Expression and localization of transforming growth factor-ß receptors type I and type II in the rat ventral prostate during regression. Mol. Endocrinol., 10: 107-115, 1996.[Abstract]
  22. Soda H., Raymond E., Shauna S., Lawrence R., Cerna C., Gomez L., Timony G. A., Von Hoff D. D., Izerbicka E. Antiproliferative effects of recombinant human bone morphogenetic protein 2 on human tumor colony-forming units. Anticancer Drugs, 9: 327-331, 1998.[Medline]



This article has been cited by other articles:


Home page
 Mol Cancer ResHome page
L. Ye, H. Kynaston, and W. G. Jiang
Bone Morphogenetic Protein-9 Induces Apoptosis in Prostate Cancer Cells, the Role of Prostate Apoptosis Response-4
Mol. Cancer Res., October 1, 2008; 6(10): 1594 - 1606.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
S. A. Khan, M. S. Nelson, C. Pan, P. M. Gaffney, and P. Gupta
Endogenous heparan sulfate and heparin modulate bone morphogenetic protein-4 signaling and activity
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1387 - C1397.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. B. Yu, D. Y. Deng, H. Beppu, C. C. Hong, C. Lai, S. A. Hoyng, N. Kawai, and K. D. Bloch
Bone Morphogenetic Protein (BMP) Type II Receptor Is Required for BMP-mediated Growth Arrest and Differentiation in Pulmonary Artery Smooth Muscle Cells
J. Biol. Chem., February 15, 2008; 283(7): 3877 - 3888.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. Jin, C. Yun, H.-S. Kim, and S.-J. Kim
TrkC Binds to the Bone Morphogenetic Protein Type II Receptor to Suppress Bone Morphogenetic Protein Signaling
Cancer Res., October 15, 2007; 67(20): 9869 - 9877.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Dai, J. Keller, J. Zhang, Y. Lu, Z. Yao, and E. T. Keller
Bone Morphogenetic Protein-6 Promotes Osteoblastic Prostate Cancer Bone Metastases through a Dual Mechanism
Cancer Res., September 15, 2005; 65(18): 8274 - 8285.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Yang, C. Zhong, B. Frenkel, A. H. Reddi, and P. Roy-Burman
Diverse Biological Effect and Smad Signaling of Bone Morphogenetic Protein 7 in Prostate Tumor Cells
Cancer Res., July 1, 2005; 65(13): 5769 - 5777.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. B. Yu, H. Beppu, N. Kawai, E. Li, and K. D. Bloch
Bone Morphogenetic Protein (BMP) Type II Receptor Deletion Reveals BMP Ligand-specific Gain of Signaling in Pulmonary Artery Smooth Muscle Cells
J. Biol. Chem., July 1, 2005; 280(26): 24443 - 24450.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
I. Y. Kim, D.-H. Lee, D. K. Lee, W. J. Kim, M. M. Kim, R. A. Morton, S. P. Lerner, and S. J. Kim
Restoration of Bone Morphogenetic Protein Receptor Type II Expression Leads to a Decreased Rate of Tumor Growth in Bladder Transitional Cell Carcinoma Cell Line TSU-Pr1
Cancer Res., October 15, 2004; 64(20): 7355 - 7360.
[Abstract] [Full Text] [PDF]

Home page
 Vet PatholHome page
T. Akiyoshi, K. Uchida, and S. Tateyama
Expression of Bone Morphogenetic Protein-6 and Bone Morphogenetic Protein Receptors in Myoepithelial Cells of Canine Mammary Gland Tumors
Vet. Pathol., March 1, 2004; 41(2): 154 - 163.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. G. Shepherd and M. W. Nachtigal
Identification of a Putative Autocrine Bone Morphogenetic Protein-Signaling Pathway in Human Ovarian Surface Epithelium and Ovarian Cancer Cells
Endocrinology, August 1, 2003; 144(8): 3306 - 3314.
[Abstract] [Full Text] [PDF]

Home page
 JBJSHome page
K. L. Weber and M. C. Gebhardt
What's New in Musculoskeletal Oncology
J. Bone Joint Surg. Am., March 31, 2003; 85(4): 761 - 767.
[Full Text] [PDF]

Home page
 Genes Dev.Home page
D. M. Panchision, J. M. Pickel, L. Studer, S.-H. Lee, P. A. Turner, T. G. Hazel, and R. D.G. McKay
Sequential actions of BMP receptors control neural precursor cell production and fate
Genes & Dev., August 15, 2001; 15(16): 2094 - 2110.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kim, I. Y.
Right arrow Articles by Morton, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, I. Y.
Right arrow Articles by Morton, R. A.

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