Cancer Research CTRC-AACR San Antonio Breast Cancer Symposium Translational Medicine Conference in Israel
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
[Cancer Research 59, 5030-5036, October 1, 1999]
© 1999 American Association for Cancer Research
This Article
Right arrow Full Text
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 Craft, N.
Right arrow Articles by L. Sawyers, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Craft, N.
Right arrow Articles by L. Sawyers, C.
[Cancer Research 59, 5030-5036, October 1, 1999]
© 1999 American Association for Cancer Research

Tumor Biology

Evidence for Clonal Outgrowth of Androgen-independent Prostate Cancer Cells from Androgen-dependent Tumors through a Two-Step Process1

Noah Craft, Chloe Chhor, Chris Tran, Arie Belldegrun, Jean DeKernion, Owen N. Witte, Jonathan Said, Robert E. Reiter and Charles L. Sawyers2

Departments of Medicine [N. C., C. C., C. T., C. L. S.], Molecular Biology Institute [N. C., O. N. W., C. L. S.], Urology [A. B., J. D., R. E. R.], Jonsson Comprehensive Cancer Center [A. B., J. D., O. N. W., J. S., R. E. R., C. L. S.], Microbiology and Molecular Genetics [O. N. W.], Howard Hughes Medical Institute [O. N. W.], and Pathology [J. S.], University of California Los Angeles, Los Angeles, California 90095-1678

Prostate cancers require androgen for growth but progress to an androgen-independent stage under the selective pressure of androgen ablation therapy. Here we describe a novel human prostate cancer xenograft (LAPC-9) propagated by serial passage in male severe combined immunodeficient mice that expresses prostate-specific antigen and wild-type androgen receptor. In response to castration, LAPC-9 cells undergo growth arrest and persist in a dormant, androgen-responsive state for at least 6 months. After prolonged periods of androgen deprivation, spontaneous androgen-independent outgrowths develop. Thus, prostate cancers progress to androgen independence through two distinct stages, initially escaping dependence on androgen for survival and, subsequently, for growth. Through the use of serial dilution and fluctuation analysis, we provide evidence that the latter stage of androgen independence results from clonal expansion of androgen-independent cells that are present at a frequency of about 1 per 105–106 androgen-dependent cells. We conclude that prostate cancers contain heterogeneous mixtures of cells that vary in their dependence on androgen for growth and survival and that treatment with antiandrogen therapy provides selective pressure and alters the relative frequency of these cells, thereby leading to outgrowths of androgen-independent cancers.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
A. Dagvadorj, S.-H. Tan, Z. Liao, L. R. Cavalli, B. R. Haddad, and M. T. Nevalainen
Androgen-Regulated and Highly Tumorigenic Human Prostate Cancer Cell Line Established from a Transplantable Primary CWR22 Tumor
Clin. Cancer Res., October 1, 2008; 14(19): 6062 - 6072.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
W. K. Hsu, M. S. Virk, B. T. Feeley, D. B. Stout, A. F. Chatziioannou, and J. R. Lieberman
Characterization of Osteolytic, Osteoblastic, and Mixed Lesions in a Prostate Cancer Mouse Model Using 18F-FDG and 18F-Fluoride PET/CT
J. Nucl. Med., March 1, 2008; 49(3): 414 - 421.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. R. Plymate, K. Haugk, I. Coleman, L. Woodke, R. Vessella, P. Nelson, R. B. Montgomery, D. L. Ludwig, and J. D. Wu
An Antibody Targeting the Type I Insulin-like Growth Factor Receptor Enhances the Castration-Induced Response in Androgen-Dependent Prostate Cancer
Clin. Cancer Res., November 1, 2007; 13(21): 6429 - 6439.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
C.-T. Wu, W.-C. Chen, S.-K. Liao, C.-L. Hsu, K.-D. Lee, and M.-F. Chen
The radiation response of hormone-resistant prostate cancer induced by long-term hormone therapy
Endocr. Relat. Cancer, September 1, 2007; 14(3): 633 - 643.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. M. Shen and C. Abate-Shen
Pten Inactivation and the Emergence of Androgen-Independent Prostate Cancer
Cancer Res., July 15, 2007; 67(14): 6535 - 6538.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Dagvadorj, S. Collins, J.-B. Jomain, J. Abdulghani, J. Karras, T. Zellweger, H. Li, M. Nurmi, K. Alanen, T. Mirtti, et al.
Autocrine Prolactin Promotes Prostate Cancer Cell Growth via Janus Kinase-2-Signal Transducer and Activator of Transcription-5a/b Signaling Pathway
Endocrinology, July 1, 2007; 148(7): 3089 - 3101.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Ilagan, J. Pottratz, K. Le, L. Zhang, S. G. Wong, R. Ayala, M. Iyer, L. Wu, S. S. Gambhir, and M. Carey
Imaging Mitogen-Activated Protein Kinase Function in Xenograft Models of Prostate Cancer.
Cancer Res., November 15, 2006; 66(22): 10778 - 10785.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. Pootrakul, R. H. Datar, S.-R. Shi, J. Cai, D. Hawes, S. G. Groshen, A. S. Lee, and R. J. Cote
Expression of Stress Response Protein Grp78 Is Associated with the Development of Castration-Resistant Prostate Cancer.
Clin. Cancer Res., October 15, 2006; 12(20): 5987 - 5993.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
H. Gao, X. Ouyang, W. A. Banach-Petrosky, M. M. Shen, and C. Abate-Shen
Emergence of Androgen Independence at Early Stages of Prostate Cancer Progression in Nkx3.1; Pten Mice
Cancer Res., August 15, 2006; 66(16): 7929 - 7933.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. Kobayashi, R. J. Barnard, S. M. Henning, D. Elashoff, S. T. Reddy, P. Cohen, P. Leung, J. Hong-Gonzalez, S. J. Freedland, J. Said, et al.
Effect of Altering Dietary {omega}-6/{omega}-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2, and Prostaglandin E2
Clin. Cancer Res., August 1, 2006; 12(15): 4662 - 4670.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
S. Gao, H. Wang, P. Lee, J. Melamed, C. X Li, F. Zhang, H. Wu, L. Zhou, and Z. Wang
Androgen receptor and prostate apoptosis response factor-4 target the c-FLIP gene to determine survival and apoptosis in the prostate gland.
J. Mol. Endocrinol., June 1, 2006; 36(3): 463 - 483.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
L. S. Lyons and K. L. Burnstein
Vav3, a Rho GTPase Guanine Nucleotide Exchange Factor, Increases during Progression to Androgen Independence in Prostate Cancer Cells and Potentiates Androgen Receptor Transcriptional Activity
Mol. Endocrinol., May 1, 2006; 20(5): 1061 - 1072.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Y. Tang, M. A. Khan, O. Goloubeva, D. I. Lee, D. Jelovac, A. M. Brodie, and A. Hussain
Docetaxel Followed by Castration Improves Outcomes in LNCaP Prostate Cancer-Bearing Severe Combined Immunodeficient Mice
Clin. Cancer Res., January 1, 2006; 12(1): 169 - 174.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. Gao, P. Lee, H. Wang, W. Gerald, M. Adler, L. Zhang, Y.-F. Wang, and Z. Wang
The Androgen Receptor Directly Targets the Cellular Fas/FasL-Associated Death Domain Protein-Like Inhibitory Protein Gene to Promote the Androgen-Independent Growth of Prostate Cancer Cells
Mol. Endocrinol., July 1, 2005; 19(7): 1792 - 1802.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Sato, M. Johnson, L. Zhang, S. S. Gambhir, M. Carey, and L. Wu
Functionality of Androgen Receptor-Based Gene Expression Imaging in Hormone Refractory Prostate Cancer
Clin. Cancer Res., May 15, 2005; 11(10): 3743 - 3749.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Z. Gu, M. A. Rubin, Y. Yang, S. E. Deprimo, H. Zhao, S. Horvath, J. D. Brooks, M. Loda, and R. E. Reiter
Reg IV: A Promising Marker of Hormone Refractory Metastatic Prostate Cancer
Clin. Cancer Res., March 15, 2005; 11(6): 2237 - 2243.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. W. Gregory, X. Fei, L. A. Ponguta, B. He, H. M. Bill, F. S. French, and E. M. Wilson
Epidermal Growth Factor Increases Coactivation of the Androgen Receptor in Recurrent Prostate Cancer
J. Biol. Chem., February 20, 2004; 279(8): 7119 - 7130.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. E. Wright, M.-J. Tsai, and R. Aebersold
Androgen Receptor Represses the Neuroendocrine Transdifferentiation Process in Prostate Cancer Cells
Mol. Endocrinol., September 1, 2003; 17(9): 1726 - 1737.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. H. Ngo, R. J. Barnard, P. Cohen, S. Freedland, C. Tran, F. deGregorio, Y. I. Elshimali, D. Heber, and W. J. Aronson
Effect of Isocaloric Low-fat Diet on Human LAPC-4 Prostate Cancer Xenografts in Severe Combined Immunodeficient Mice and the Insulin-like Growth Factor Axis
Clin. Cancer Res., July 1, 2003; 9(7): 2734 - 2743.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y.-P. Lee, E. M. Schwarz, M. Davies, M. Jo, J. Gates, X. Zhang, J. Wu, and J. R. Lieberman
Use of Zoledronate to Treat Osteoblastic versus Osteolytic Lesions in a Severe-Combined-Immunodeficient Mouse Model
Cancer Res., October 1, 2002; 62(19): 5564 - 5570.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
A. Jain, A. Lam, I. Vivanco, M. F. Carey, and R. E. Reiter
Identification of an Androgen-Dependent Enhancer within the Prostate Stem Cell Antigen Gene
Mol. Endocrinol., October 1, 2002; 16(10): 2323 - 2337.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
I. K. Mellinghoff, C. Tran, and C. L. Sawyers
Growth Inhibitory Effects of the Dual ErbB1/ErbB2 Tyrosine Kinase Inhibitor PKI-166 on Human Prostate Cancer Xenografts
Cancer Res., September 15, 2002; 62(18): 5254 - 5259.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. D. Sadar, V. A. Akopian, and E. Beraldi
Characterization of a New in Vivo Hollow Fiber Model for the Study of Progression of Prostate Cancer to Androgen Independence
Mol. Cancer Ther., June 1, 2002; 1(8): 629 - 637.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. D. Chen and C. L. Sawyers
NF-{kappa}B Activates Prostate-Specific Antigen Expression and Is Upregulated in Androgen-Independent Prostate Cancer
Mol. Cell. Biol., April 15, 2002; 22(8): 2862 - 2870.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
M. E. Grossmann, H. Huang, and D. J. Tindall
Androgen Receptor Signaling in Androgen-Refractory Prostate Cancer
J Natl Cancer Inst, November 21, 2001; 93(22): 1687 - 1697.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Long. G. Wang, L. Ossowski, and A. C. Ferrari
Overexpressed Androgen Receptor Linked to p21WAF1 Silencing May Be Responsible for Androgen Independence and Resistance to Apoptosis of a Prostate Cancer Cell Line
Cancer Res., October 1, 2001; 61(20): 7544 - 7551.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. S. Neshat, I. K. Mellinghoff, C. Tran, B. Stiles, G. Thomas, R. Petersen, P. Frost, J. J. Gibbons, H. Wu, and C. L. Sawyers
Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR
PNAS, August 10, 2001; (2001) 171076798.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Nickerson, F. Chang, D. Lorimer, S. P. Smeekens, C. L. Sawyers, and M. Pollak
In Vivo Progression of LAPC-9 and LNCaP Prostate Cancer Models to Androgen Independence Is Associated with Increased Expression of Insulin-like Growth Factor I (IGF-I) and IGF-I Receptor (IGF-IR)
Cancer Res., August 1, 2001; 61(16): 6276 - 6280.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
G. de Pinieux, M.-E. Legrier, F. Poirson-Bichat, Y. Courty, R. Bras-Goncalves, A.-M. Dutrillaux, F. Nemati, S. Oudard, R. Lidereau, P. Broqua, et al.
Clinical and Experimental Progression of a New Model of Human Prostate Cancer and Therapeutic Approach
Am. J. Pathol., August 1, 2001; 159(2): 753 - 764.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
A. T. Weeraratna, S. L. Dalrymple, J. C. Lamb, S. R. Denmeade, S. Miknyoczki, C. A. Dionne, and J. T. Isaacs
Pan-trk Inhibition Decreases Metastasis and Enhances Host Survival in Experimental Models as a Result of Its Selective Induction of Apoptosis of Prostate Cancer Cells
Clin. Cancer Res., August 1, 2001; 7(8): 2237 - 2245.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. W. Gregory, R. T. Johnson Jr., J. L. Mohler, F. S. French, and E. M. Wilson
Androgen Receptor Stabilization in Recurrent Prostate Cancer Is Associated with Hypersensitivity to Low Androgen
Cancer Res., April 1, 2001; 61(7): 2892 - 2898.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
D. E. H. Afar, I. Vivanco, R. S. Hubert, J. Kuo, E. Chen, D. C. Saffran, A. B. Raitano, and A. Jakobovits
Catalytic Cleavage of the Androgen-regulated TMPRSS2 Protease Results in Its Secretion by Prostate and Prostate Cancer Epithelia
Cancer Res., February 1, 2001; 61(4): 1686 - 1692.
[Abstract] [Full Text]

Home page
 JNCI J Natl Cancer InstHome page
H. I. Scher
HER2 in Prostate Cancer--a Viable Target or Innocent Bystander?
J Natl Cancer Inst, December 6, 2000; 92(23): 1866 - 1868.
[Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
S. Signoretti, R. Montironi, J. Manola, A. Altimari, C. Tam, G. Bubley, S. Balk, G. Thomas, I. Kaplan, L. Hlatky, et al.
Her-2-neu Expression and Progression Toward Androgen Independence in Human Prostate Cancer
J Natl Cancer Inst, December 6, 2000; 92(23): 1918 - 1925.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. C. Amler, D. B. Agus, C. LeDuc, M. L. Sapinoso, W. D. Fox, S. Kern, D. Lee, V. Wang, M. Leysens, B. Higgins, et al.
Dysregulated Expression of Androgen-responsive and Nonresponsive Genes in the Androgen-independent Prostate Cancer Xenograft Model CWR22-R
Cancer Res., November 1, 2000; 60(21): 6134 - 6141.
[Abstract] [Full Text]

Home page
 Genes Dev.Home page
C. Abate-Shen and M. M. Shen
Molecular genetics of prostate cancer
Genes & Dev., October 1, 2000; 14(19): 2410 - 2434.
[Full Text]

Home page
 JNCI J Natl Cancer InstHome page
J. T. Isaacs
Apoptosis: Translating Theory to Therapy for Prostate Cancer
J Natl Cancer Inst, September 6, 2000; 92(17): 1367 - 1369.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. C. Saffran, A. B. Raitano, R. S. Hubert, O. N. Witte, R. E. Reiter, and A. Jakobovits
Anti-PSCA mAbs inhibit tumor growth and metastasis formation and prolong the survival of mice bearing human prostate cancer xenografts
PNAS, February 27, 2001; 98(5): 2658 - 2663.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. S. Neshat, I. K. Mellinghoff, C. Tran, B. Stiles, G. Thomas, R. Petersen, P. Frost, J. J. Gibbons, H. Wu, and C. L. Sawyers
Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR
PNAS, August 28, 2001; 98(18): 10314 - 10319.
[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
Copyright © 1999 by the American Association for Cancer Research.