help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kokontis, J. M.
Right arrow Articles by Liao, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kokontis, J. M.
Right arrow Articles by Liao, S.
Molecular Endocrinology 12 (7): 941-953
Copyright © 1998 by The Endocrine Society

Progression of LNCaP Prostate Tumor Cells during Androgen Deprivation: Hormone-Independent Growth, Repression of Proliferation by Androgen, and Role for p27Kip1 in Androgen-Induced Cell Cycle Arrest

John M. Kokontis, Nissim Hay1 and Shutsung Liao

The Ben May Institute for Cancer Research (J.M.K., N.H., S.L.) The Departments of Pharmacology and Physiology (N.H.) and Biochemistry and Molecular Biology (S.L.) The University of Chicago Chicago, Illinois 60637

The molecular mechanism of androgen-independent growth of prostate cancer after androgen ablation was explored in LNCaP cells. An androgen-dependent clonal subline of the LNCaP human prostate carcinoma cell line, LNCaP 104-S, progressed to a slow growing stage (104-R1) and then to a faster growing stage (104-R2) during more than 2 yr of continuous culture in the absence of androgen. Androgen-induced proliferation of 104-S cells is inhibited by the antiandrogen Casodex, while proliferation of 104-R1 and 104-R2 cells is unaffected by Casodex. This indicates that proliferation of 104-R1 and 104-R2 cells is not supported by low levels of androgen in the culture medium. Compared with LNCaP 104-S cells, both 104-R1 and 104-R2 cells express higher basal levels of androgen receptor (AR), and proliferation of these two cell lines is paradoxically repressed by androgen. After continuous passage in androgen-containing medium, 104-R1 cells reverted back to an androgen-dependent phenotype. The mechanism of androgenic repression of 104-R1 and 104-R2 sublines was further evaluated by examining the role of critical regulatory factors involved in the control of cell cycle progression. At concentrations that repressed growth, androgen transiently induced the expression of the cyclin-dependent kinase (cdk) inhibitor p21waf1/cip1 in 104-R1 cells, while expression of the cdk inhibitor p27Kip1 was persistently induced by androgen in both 104-R1 and 104-R2 cells. Induced expression of murine p27Kip1 in 104-R2 cells resulted in G1 arrest. Specific immunoprecipitates of Cdk2 but not Cdk4 from androgen-treated 104-R1 cells contained both p21waf1/cip1 and p27Kip1. This observation was confirmed by in vitro assay of histone H1 and Rb (retinoblastoma protein) phosphorylation by the proteins associated with the immune complex. Furthermore, inhibition of Cdk2 activity correlated with the accumulation of p27Kip1 and not p21waf1/cip1. From these results we conclude that androgenic repression of LNCaP 104-R1 and 104-R2 cell proliferation is due to the induction of p27Kip1, which in turn inhibits Cdk2, a factor critical for cell cycle progression and proliferation.




This article has been cited by other articles:


Home page
 Endocr Relat CancerHome page
J. M D'Antonio, D. J Vander Griend, and J. T Isaacs
DNA licensing as a novel androgen receptor mediated therapeutic target for prostate cancer
Endocr. Relat. Cancer, June 1, 2009; 16(2): 325 - 332.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Sun, Q. Wang, S. Balk, M. Brown, G.-S. M. Lee, and P. Kantoff
The Role of microRNA-221 and microRNA-222 in Androgen-Independent Prostate Cancer Cell Lines
Cancer Res., April 15, 2009; 69(8): 3356 - 3363.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
C.-L. Hsieh, C. Cai, A. Giwa, A. Bivins, S.-Y. Chen, D. Sabry, K. Govardhan, and L. Shemshedini
Expression of a hyperactive androgen receptor leads to androgen-independent growth of prostate cancer cells
J. Mol. Endocrinol., July 1, 2008; 41(1): 13 - 23.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Bagchi, J. Wu, J. French, J. Kim, N. H. Moniri, and Y. Daaka
Androgens Transduce the G{alpha}s-Mediated Activation of Protein Kinase A in Prostate Cells
Cancer Res., May 1, 2008; 68(9): 3225 - 3231.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
P. Mathew
Prolonged control of progressive castration-resistant metastatic prostate cancer with testosterone replacement therapy: the case for a prospective trial
Ann. Onc., February 1, 2008; 19(2): 395 - 396.
[Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. H. Kim, J. M. Lee, H. J. Nam, H. J. Choi, J. W. Yang, J. S. Lee, M. H. Kim, S.-I. Kim, C. H. Chung, K. I. Kim, et al.
SUMOylation of pontin chromatin-remodeling complex reveals a signal integration code in prostate cancer cells
PNAS, December 26, 2007; 104(52): 20793 - 20798.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
L. Leotoing, M. Manin, D. Monte, S. Baron, Y. Communal, C. Lours, G. Veyssiere, L. Morel, and C. Beaudoin
Crosstalk between androgen receptor and epidermal growth factor receptor-signalling pathways: a molecular switch for epithelial cell differentiation
J. Mol. Endocrinol., August 1, 2007; 39(2): 151 - 162.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Srinivasan, R. S. Ranga, R. Burikhanov, S.-S. Han, and D. Chendil
Par-4-Dependent Apoptosis by the Dietary Compound Withaferin A in Prostate Cancer Cells
Cancer Res., January 1, 2007; 67(1): 246 - 253.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
X. Yuan, T. Li, H. Wang, T. Zhang, M. Barua, R. A. Borgesi, G. J. Bubley, M. L. Lu, and S. P. Balk
Androgen Receptor Remains Critical for Cell-Cycle Progression in Androgen-Independent CWR22 Prostate Cancer Cells
Am. J. Pathol., August 1, 2006; 169(2): 682 - 696.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C.-p. Chuu, R. A. Hiipakka, J. M. Kokontis, J. Fukuchi, R.-Y. Chen, and S. Liao
Inhibition of Tumor Growth and Progression of LNCaP Prostate Cancer Cells in Athymic Mice by Androgen and Liver X Receptor Agonist.
Cancer Res., July 1, 2006; 66(13): 6482 - 6486.
[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
 Mol. Cell. Biol.Home page
Y. Lin, J. Kokontis, F. Tang, B. Godfrey, S. Liao, A. Lin, Y. Chen, and J. Xiang
Androgen and its receptor promote bax-mediated apoptosis.
Mol. Cell. Biol., March 1, 2006; 26(5): 1908 - 1916.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. D. Debes, B. Comuzzi, L. J. Schmidt, S. M. Dehm, Z. Culig, and D. J. Tindall
p300 Regulates Androgen Receptor-Independent Expression of Prostate-Specific Antigen in Prostate Cancer Cells Treated Chronically with Interleukin-6
Cancer Res., July 1, 2005; 65(13): 5965 - 5973.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
P.-F. Hung, B.-T. Wu, H.-C. Chen, Y.-H. Chen, C.-L. Chen, M.-H. Wu, H.-C. Liu, M.-J. Lee, and Y.-H. Kao
Antimitogenic effect of green tea (-)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the ERK and Cdk2 pathways
Am J Physiol Cell Physiol, May 1, 2005; 288(5): C1094 - C1108.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
Y.-H. Chen, P.-F. Hung, and Y.-H. Kao
IGF-I downregulates resistin gene expression and protein secretion
Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E1019 - E1027.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C.-p. Chuu, R. A. Hiipakka, J. Fukuchi, J. M. Kokontis, and S. Liao
Androgen Causes Growth Suppression and Reversion of Androgen-Independent Prostate Cancer Xenografts to an Androgen-Stimulated Phenotype in Athymic Mice
Cancer Res., March 15, 2005; 65(6): 2082 - 2084.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T.-L. Cha, L. Qiu, C.-T. Chen, Y. Wen, and M.-C. Hung
Emodin Down-Regulates Androgen Receptor and Inhibits Prostate Cancer Cell Growth
Cancer Res., March 15, 2005; 65(6): 2287 - 2295.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Fukuchi, R. A. Hiipakka, J. M. Kokontis, S. Hsu, A. L. Ko, M. L. Fitzgerald, and S. Liao
Androgenic Suppression of ATP-binding Cassette Transporter A1 Expression in LNCaP Human Prostate Cancer Cells
Cancer Res., November 1, 2004; 64(21): 7682 - 7685.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Fukuchi, J. M. Kokontis, R. A. Hiipakka, C.-p. Chuu, and S. Liao
Antiproliferative Effect of Liver X Receptor Agonists on LNCaP Human Prostate Cancer Cells
Cancer Res., November 1, 2004; 64(21): 7686 - 7689.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Hara, K. Nakamura, H. Araki, M. Kusaka, and M. Yamaoka
Enhanced Androgen Receptor Signaling Correlates with the Androgen-refractory Growth in a Newly Established MDA PCa 2b-hr Human Prostate Cancer Cell Subline
Cancer Res., September 1, 2003; 63(17): 5622 - 5628.
[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
 EndocrinologyHome page
M. V. Maffini, P. Geck, C. E. Powell, C. Sonnenschein, and A. M. Soto
Mechanism of Androgen Action on Cell Proliferation: AS3 Protein as a Mediator of Proliferative Arrest in the Rat Prostate
Endocrinology, July 1, 2002; 143(7): 2708 - 2714.
[Abstract] [Full Text] [PDF]

Home page
 Cell Growth Differ.Home page
D. C. Whitacre, S. Chauhan, T. Davis, D. Gordon, A. E. Cress, and R. L. Miesfeld
Androgen Induction of in Vitro Prostate Cell Differentiation
Cell Growth Differ., January 1, 2002; 13(1): 1 - 11.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
A. M. Soto and C. Sonnenschein
The Two Faces of Janus: Sex Steroids as Mediators of Both Cell Proliferation and Cell Death
J Natl Cancer Inst, November 21, 2001; 93(22): 1673 - 1675.
[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
 EndocrinologyHome page
H. Murillo, H. Huang, L. J. Schmidt, D. I. Smith, and D. J. Tindall
Role of PI3K Signaling in Survival and Progression of LNCaP Prostate Cancer Cells to the Androgen Refractory State
Endocrinology, November 1, 2001; 142(11): 4795 - 4805.
[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. Stanbrough, I. Leav, P. W. L. Kwan, G. J. Bubley, and S. P. Balk
Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium
PNAS, September 4, 2001; (2001) 191235898.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Hobisch, R. Ramoner, D. Fuchs, S. Godoy-Tundidor, G. Bartsch, H. Klocker, and Z. Culig
Prostate Cancer Cells (LNCaP) Generated after Long-Term Interleukin 6 (IL-6) Treatment Express IL-6 and Acquire an IL-6 Partially Resistant Phenotype
Clin. Cancer Res., September 1, 2001; 7(9): 2941 - 2948.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
D. Waltregny, I. Leav, S. Signoretti, P. Soung, D. Lin, F. Merk, J. Y. Adams, N. Bhattacharya, N. Cirenei, and M. Loda
Androgen-Driven Prostate Epithelial Cell Proliferation and Differentiation in Vivo Involve the Regulation of p27
Mol. Endocrinol., May 1, 2001; 15(5): 765 - 782.
[Abstract] [Full Text]

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
B. Lin, J. T. White, C. Ferguson, S. Wang, R. Vessella, R. Bumgarner, L. D. True, L. Hood, and P. S. Nelson
Prostate Short-Chain Dehydrogenase Reductase 1 (PSDR1): A New Member of the Short-Chain Steroid Dehydrogenase/Reductase Family Highly Expressed in Normal and Neoplastic Prostate Epithelium
Cancer Res., February 1, 2001; 61(4): 1611 - 1618.
[Abstract] [Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. Geck, M. V. Maffini, J. Szelei, C. Sonnenschein, and A. M. Soto
Androgen-induced proliferative quiescence in prostate cancer cells: The role of AS3 as its mediator
PNAS, August 29, 2000; 97(18): 10185 - 10190.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
A. Yamamoto, Y. Hashimoto, K. Kohri, E. Ogata, S.-a. Kato, K. Ikeda, and M. Nakanishi
Cyclin E as a Coactivator of the Androgen Receptor
J. Cell Biol., August 21, 2000; 150(4): 873 - 880.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
R. K. Tyagi, Y. Lavrovsky, S. C. Ahn, C. S. Song, B. Chatterjee, and A. K. Roy
Dynamics of Intracellular Movement and Nucleocytoplasmic Recycling of the Ligand-Activated Androgen Receptor in Living Cells
Mol. Endocrinol., August 1, 2000; 14(8): 1162 - 1174.
[Abstract] [Full Text]

Home page
 EndocrinologyHome page
X.-Y. Zhao, D. M. Peehl, N. M. Navone, and D. Feldman
1{alpha},25-Dihydroxyvitamin D3 Inhibits Prostate Cancer Cell Growth by Androgen-Dependent and Androgen-Independent Mechanisms
Endocrinology, July 1, 2000; 141(7): 2548 - 2556.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. Shen, M. Sumitomo, J. Dai, A. Harris, D. Kaminetzky, M. Gao, K. L. Burnstein, and D. M. Nanus
Androgen-Induced Growth Inhibition of Androgen Receptor Expressing Androgen-Independent Prostate Cancer Cells Is Mediated by Increased Levels of Neutral Endopeptidase
Endocrinology, May 1, 2000; 141(5): 1699 - 1704.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Kimura and E. P. Gelmann
Tumor Necrosis Factor-alpha and Fas Activate Complementary Fas-associated Death Domain-dependent Pathways That Enhance Apoptosis Induced by gamma -Irradiation
J. Biol. Chem., March 17, 2000; 275(12): 8610 - 8617.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
W.-S. Shim, M. Conaway, S. Masamura, W. Yue, J.-P. Wang, R. Kumar, and R. J. Santen
Estradiol Hypersensitivity and Mitogen-Activated Protein Kinase Expression in Long-Term Estrogen Deprived Human Breast Cancer Cells in Vivo
Endocrinology, January 1, 2000; 141(1): 396 - 405.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
D. B. Agus, C. Cordon-Cardo, W. Fox, M. Drobnjak, A. Koff, D. W. Golde, and H. I. Scher
Prostate Cancer Cell Cycle Regulators: Response to Androgen Withdrawal and Development of Androgen Independence
J Natl Cancer Inst, November 3, 1999; 91(21): 1869 - 1876.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. M. Grad, J. Le Dai, S. Wu, and K. L. Burnstein
Multiple Androgen Response Elements and a Myc Consensus Site in the Androgen Receptor (AR) Coding Region Are Involved in Androgen-Mediated Up-Regulation of AR Messenger RNA
Mol. Endocrinol., November 1, 1999; 13(11): 1896 - 1911.
[Abstract] [Full Text]

Home page
 Clin. Cancer Res.Home page
C. T. Lee, P. Capodieci, I. Osman, M. Fazzari, J. Ferrara, H. I. Scher, and C. Cordon-Cardo
Overexpression of the Cyclin-dependent Kinase Inhibitor p16 Is Associated with Tumor Recurrence in Human Prostate Cancer
Clin. Cancer Res., May 1, 1999; 5(5): 977 - 983.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
X.-Y. Zhao, L. H. Ly, D. M. Peehl, and D. Feldman
Induction of Androgen Receptor by 1{alpha},25-Dihydroxyvitamin D3 and 9-cis Retinoic Acid in LNCaP Human Prostate Cancer Cells
Endocrinology, March 1, 1999; 140(3): 1205 - 1212.
[Abstract] [Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Yeh, Y.-C. Hu, M. Rahman, H.-K. Lin, C.-L. Hsu, H.-J. Ting, H.-Y. Kang, and C. Chang
Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells
PNAS, October 10, 2000; 97(21): 11256 - 11261.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Stanbrough, I. Leav, P. W. L. Kwan, G. J. Bubley, and S. P. Balk
Prostatic intraepithelial neoplasia in mice expressing an androgen receptor transgene in prostate epithelium
PNAS, September 11, 2001; 98(19): 10823 - 10828.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1998 by The Endocrine Society