| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 7, 5209-5218, February 15, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Medicine/Endocrinology and the
§ Department of Obstetrics and Gynecology and Department of
Pharmaceutical Science, University of Colorado School of Medicine,
Denver, Colorado 80262
The PR-A and PR-B isoforms of progesterone
receptors (PR) have different physiological functions, and their ratio
varies widely in breast cancers. To determine whether the two PR
regulate different genes, we used human breast cancer cell lines
engineered to express one or the other isoform. Cells were treated with
progesterone in triplicate, time-separated experiments, allowing
statistical analyses of microarray gene expression data. Of 94 progesterone-regulated genes, 65 are uniquely regulated by PR-B, 4 uniquely by PR-A, and only 25 by both. Almost half the genes encode
proteins that are membrane-bound or involved in membrane-initiated
signaling. We also find an important set of progesterone-regulated
genes involved in mammary gland development and/or implicated in breast cancer. This first, large scale study of PR gene regulation has important implications for the measurement of PR in breast cancers and
for the many clinical uses of synthetic progestins. It suggests that it
is important to distinguish between the two isoforms in breast cancers
and that isoform-specific genes can be used to screen for ligands that
selectively modulate the activity of PR-A or PR-B. Additionally, use of
natural target genes, rather than "consensus" response elements,
for transcription studies should improve our understanding of steroid
hormone action.
Differential Gene Regulation by the Two Progesterone Receptor
Isoforms in Human Breast Cancer Cells*
,
*
This work was supported by National Institutes of Health
Grants DK48238 and CA26869, the National Foundation for Cancer Research (to K. B. H.), Department of Defense Breast Cancer Research Program Concept Award BC996535 (to J. K. R.), and an American Cancer Society IRG University of Colorado Cancer Center Seed Grant (to J. K. R.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of
Medicine/Endocrinology, University of Colorado School of Medicine, Box B-151, 4200 East Ninth Ave., Denver, CO 80262. Tel.: 303-315-8443; Fax:
303-315-4525; E-mail: jennifer.richer@uchsc.edu;
www.khorwitzlab.org.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. H. Ibrahim, S. A. Byron, X. Cui, A. V. Lee, and D. Yee Progesterone Receptor-B Regulation of Insulin-Like Growth Factor-Stimulated Cell Migration in Breast Cancer Cells via Insulin Receptor Substrate-2 Mol. Cancer Res., September 1, 2008; 6(9): 1491 - 1498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Diergaarde, J. D. Potter, E. R. Jupe, S. Manjeshwar, C. D. Shimasaki, T. W. Pugh, D. C. DeFreese, B. A. Gramling, I. Evans, and E. White Polymorphisms in Genes Involved in Sex Hormone Metabolism, Estrogen Plus Progestin Hormone Therapy Use, and Risk of Postmenopausal Breast Cancer Cancer Epidemiol. Biomarkers Prev., July 1, 2008; 17(7): 1751 - 1759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Glaser, S. DeMorrow, H. Francis, Y. Ueno, E. Gaudio, S. Vaculin, J. Venter, A. Franchitto, P. Onori, B. Vaculin, et al. Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms Am J Physiol Gastrointest Liver Physiol, July 1, 2008; 295(1): G124 - G136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mani Progestin Receptor Subtypes in the Brain: The Known and the Unknown Endocrinology, June 1, 2008; 149(6): 2750 - 2756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Tompkins, T. L. Sit, and A. D. Wallace Unique Transcription Start Sites and Distinct Promoter Regions Differentiate the Pregnane X Receptor (PXR) Isoforms PXR 1 and PXR 2 Drug Metab. Dispos., May 1, 2008; 36(5): 923 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Aoyagi and T. K. Archer Nicotinamide Uncouples Hormone-Dependent Chromatin Remodeling from Transcription Complex Assembly Mol. Cell. Biol., January 1, 2008; 28(1): 30 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Santos, S. Z. Haslam, and S. E. Conrad Estrogen and Progesterone are Critical Regulators of Stat5a Expression in the Mouse Mammary Gland Endocrinology, January 1, 2008; 149(1): 329 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Daniel, E. J. Faivre, and C. A. Lange Phosphorylation-Dependent Antagonism of Sumoylation Derepresses Progesterone Receptor Action in Breast Cancer Cells Mol. Endocrinol., December 1, 2007; 21(12): 2890 - 2906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kowase, H. E. Walsh, D. S. Darling, and M. A. Shupnik Estrogen Enhances Gonadotropin-Releasing Hormone-Stimulated Transcription of the Luteinizing Hormone Subunit Promoters via Altered Expression of Stimulatory and Suppressive Transcription Factors Endocrinology, December 1, 2007; 148(12): 6083 - 6091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Liu, H. Matsuo, J. B. Laoag-Fernandez, Q. Xu, and T. Maruo The effects of progesterone on apoptosis in the human trophoblast-derived HTR-8/SV neo cells Mol. Hum. Reprod., December 1, 2007; 13(12): 869 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. McGowan, A. J. Russell, V. Boonyaratanakornkit, D. N. Saunders, G. M. Lehrbach, C. M. Sergio, E. A. Musgrove, D. P. Edwards, and R. L. Sutherland Progestins Reinitiate Cell Cycle Progression in Antiestrogen-Arrested Breast Cancer Cells through the B-Isoform of Progesterone Receptor Cancer Res., September 15, 2007; 67(18): 8942 - 8951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-W. Jeong, K. Y. Lee, S. J. Han, B. J. Aronow, J. P. Lydon, B. W. O'Malley, and F. J. DeMayo The p160 Steroid Receptor Coactivator 2, SRC-2, Regulates Murine Endometrial Function and Regulates Progesterone-Independent and -Dependent Gene Expression Endocrinology, September 1, 2007; 148(9): 4238 - 4250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System Endocr. Rev., June 1, 2007; 28(4): 387 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Merlino, T. N. Welsh, H. Tan, L. J. Yi, V. Cannon, B. M. Mercer, and S. Mesiano Nuclear Progesterone Receptors in the Human Pregnancy Myometrium: Evidence that Parturition Involves Functional Progesterone Withdrawal Mediated by Increased Expression of Progesterone Receptor-A J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1927 - 1933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. Madauss, E. T. Grygielko, S.-J. Deng, A. C. Sulpizio, T. B. Stanley, C. Wu, S. A. Short, S. K. Thompson, E. L. Stewart, N. J. Laping, et al. A Structural and in Vitro Characterization of Asoprisnil: A Selective Progesterone Receptor Modulator Mol. Endocrinol., May 1, 2007; 21(5): 1066 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Aoyagi and T. K. Archer Dynamic Histone Acetylation/Deacetylation with Progesterone Receptor-Mediated Transcription Mol. Endocrinol., April 1, 2007; 21(4): 843 - 856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Shatnawi, T. Tran, and M. Ratnam R5020 and RU486 Act as Progesterone Receptor Agonists to Enhance Sp1/Sp4-Dependent Gene Transcription by an Indirect Mechanism Mol. Endocrinol., March 1, 2007; 21(3): 635 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Connaghan-Jones, A. F. Heneghan, M. T. Miura, and D. L. Bain Thermodynamic analysis of progesterone receptor-promoter interactions reveals a molecular model for isoform-specific function PNAS, February 13, 2007; 104(7): 2187 - 2192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Romano, B. Delvoux, D.-C. Fischer, and P. Groothuis The PROGINS polymorphism of the human progesterone receptor diminishes the response to progesterone J. Mol. Endocrinol., February 1, 2007; 38(2): 331 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Boonyaratanakornkit, E. McGowan, L. Sherman, M. A. Mancini, B. J. Cheskis, and D. P. Edwards The Role of Extranuclear Signaling Actions of Progesterone Receptor in Mediating Progesterone Regulation of Gene Expression and the Cell Cycle Mol. Endocrinol., February 1, 2007; 21(2): 359 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Faivre and C. A. Lange Progesterone Receptors Upregulate Wnt-1 To Induce Epidermal Growth Factor Receptor Transactivation and c-Src-Dependent Sustained Activation of Erk1/2 Mitogen-Activated Protein Kinase in Breast Cancer Cells Mol. Cell. Biol., January 15, 2007; 27(2): 466 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Z. Lu, S. E. Wardell, K. L. Burnstein, D. Defranco, P. J. Fuller, V. Giguere, R. B. Hochberg, L. McKay, J.-M. Renoir, N. L. Weigel, et al. International Union of Pharmacology. LXV. The Pharmacology and Classification of the Nuclear Receptor Superfamily: Glucocorticoid, Mineralocorticoid, Progesterone, and Androgen Receptors Pharmacol. Rev., December 1, 2006; 58(4): 782 - 797. [Full Text] [PDF]
|
|
|
|
|
|
P. A. Mote, R. L. Arnett-Mansfield, N. Gava, A. deFazio, B. Mulac-Jericevic, O. M. Conneely, and C. L. Clarke Overlapping and Distinct Expression of Progesterone Receptors A and B in Mouse Uterus and Mammary Gland during the Estrous Cycle Endocrinology, December 1, 2006; 147(12): 5503 - 5512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Man, H.-Y. Li, P.-J. Zhang, T. Zhou, K. He, X. Pan, B. Liang, A.-L. Li, J. Zhao, W.-L. Gong, et al. PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus Nucleic Acids Res., November 14, 2006; 34(19): 5552 - 5566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tung, H. Abdel-Hafiz, T. Shen, D. M. E. Harvell, L. K. Nitao, J. K. Richer, C. A. Sartorius, G. S. Takimoto, and K. B. Horwitz Progesterone Receptors (PR)-B and -A Regulate Transcription by Different Mechanisms: AF-3 Exerts Regulatory Control over Coactivator Binding to PR-B Mol. Endocrinol., November 1, 2006; 20(11): 2656 - 2670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Brayman, J. Julian, B. Mulac-Jericevic, O. M. Conneely, D. P. Edwards, and D. D. Carson Progesterone Receptor Isoforms A and B Differentially Regulate MUC1 Expression in Uterine Epithelial Cells Mol. Endocrinol., October 1, 2006; 20(10): 2278 - 2291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Liang, Y. Li, X. Be, S. Howes, and W. Liu Detecting and profiling tissue-selective genes Physiol Genomics, September 14, 2006; 26(2): 158 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L Turgeon and D. W Waring Differential expression and regulation of progesterone receptor isoforms in rat and mouse pituitary cells and L{beta}T2 gonadotropes. J. Endocrinol., September 1, 2006; 190(3): 837 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Georgiakaki, N. Chabbert-Buffet, B. Dasen, G. Meduri, S. Wenk, L. Rajhi, L. Amazit, A. Chauchereau, C. W. Burger, L. J. Blok, et al. Ligand-Controlled Interaction of Histone Acetyltransferase Binding to ORC-1 (HBO1) with the N-Terminal Transactivating Domain of Progesterone Receptor Induces Steroid Receptor Coactivator 1-Dependent Coactivation of Transcription Mol. Endocrinol., September 1, 2006; 20(9): 2122 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Spoelstra, N. G. Manning, Y. Higashi, D. Darling, M. Singh, K. R. Shroyer, R. R. Broaddus, K. B. Horwitz, and J. K. Richer The Transcription Factor ZEB1 Is Aberrantly Expressed in Aggressive Uterine Cancers. Cancer Res., April 1, 2006; 66(7): 3893 - 3902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Velarde, M. Iruthayanathan, R. R. Eason, D. Zhang, F. A. Simmen, and R. C. M. Simmen Progesterone Receptor Transactivation of the Secretory Leukocyte Protease Inhibitor Gene in Ishikawa Endometrial Epithelial Cells Involves Recruitment of Kruppel-Like Factor 9/Basic Transcription Element Binding Protein-1 Endocrinology, April 1, 2006; 147(4): 1969 - 1978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Huggins, J. Y.Y. Wong, S. E. Hankinson, and I. De Vivo GATA5 Activation of the Progesterone Receptor Gene Promoter in Breast Cancer Cells Is Influenced by the +331G/A Polymorphism Cancer Res., February 1, 2006; 66(3): 1384 - 1390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ma, P. Katiyar, L. P. Jones, S. Fan, Y. Zhang, P. A. Furth, and E. M. Rosen The Breast Cancer Susceptibility Gene BRCA1 Regulates Progesterone Receptor Signaling in Mammary Epithelial Cells Mol. Endocrinol., January 1, 2006; 20(1): 14 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Sartorius, D. M.E. Harvell, T. Shen, and K. B. Horwitz Progestins Initiate a Luminal to Myoepithelial Switch in Estrogen-Dependent Human Breast Tumors without Altering Growth Cancer Res., November 1, 2005; 65(21): 9779 - 9788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Graham, M. L. Yager, H. D. Hill, K. Byth, G. M. O'Neill, and C. L. Clarke Altered Progesterone Receptor Isoform Expression Remodels Progestin Responsiveness of Breast Cancer Cells Mol. Endocrinol., November 1, 2005; 19(11): 2713 - 2735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Stephens, H. Han, V. Gokhale, and D. D. Von Hoff PRL phosphatases as potential molecular targets in cancer Mol. Cancer Ther., November 1, 2005; 4(11): 1653 - 1661. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Colozza, D. Larsimont, and M.J. Piccart Progesterone Receptor Testing: Not the Right Time to Be Buried J. Clin. Oncol., June 1, 2005; 23(16): 3867 - 3868. [Full Text] [PDF]
|
|
|
|
 |
|
 I. Balogh, S. Hafizi, J. Stenhoff, K. Hansson, and B. Dahlback Analysis of Gas6 in Human Platelets and Plasma Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1280 - 1286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Hanekamp, S. C.J.P. Gielen, P. E. De Ruiter, S. Chadha-Ajwani, F. J. Huikeshoven, C. W. Burger, J. A. Grootegoed, and L. J. Blok Differences in Invasive Capacity of Endometrial Cancer Cell Lines Expressing Different Progesterone Receptor Isotypes: Possible Involvement of Cadherins Reproductive Sciences, May 1, 2005; 12(4): 278 - 284. [Abstract] [PDF]
|
|
|
|
|
|
E. Smid-Koopman, L. C. M. Kuhne, E. E. Hanekamp, S. C.J.P. Gielen, P. E. De Ruiter, J. A. Grootegoed, T. J.M. Helmerhorst, C. W. Burger, A. O. Brinkmann, F. J. Huikeshoven, et al. Progesterone-Induced Inhibition of Growth and Differential Regulation of Gene Expression in PRA- and/or PRB-Expressing Endometrial Cancer Cell Lines Reproductive Sciences, May 1, 2005; 12(4): 285 - 292. [Abstract] [PDF]
|
|
|
|
|
|
K. Chwalisz, M. C. Perez, D. DeManno, C. Winkel, G. Schubert, and W. Elger Selective Progesterone Receptor Modulator Development and Use in the Treatment of Leiomyomata and Endometriosis Endocr. Rev., May 1, 2005; 26(3): 423 - 438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Narayanan, D. P. Edwards, and N. L. Weigel Human Progesterone Receptor Displays Cell Cycle-Dependent Changes in Transcriptional Activity Mol. Cell. Biol., April 15, 2005; 25(8): 2885 - 2898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fritah, C. Saucier, J. Mester, G. Redeuilh, and M. Sabbah p21WAF1/CIP1 Selectively Controls the Transcriptional Activity of Estrogen Receptor {alpha} Mol. Cell. Biol., March 15, 2005; 25(6): 2419 - 2430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Jacobsen, S. A. Schittone, J. K. Richer, and K. B. Horwitz Progesterone-Independent Effects of Human Progesterone Receptors (PRs) in Estrogen Receptor-Positive Breast Cancer: PR Isoform-Specific Gene Regulation and Tumor Biology Mol. Endocrinol., March 1, 2005; 19(3): 574 - 587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wu, S. Brandt, and S. M. Hyder Ligand- and Cell-Specific Effects of Signal Transduction Pathway Inhibitors on Progestin-Induced Vascular Endothelial Growth Factor Levels in Human Breast Cancer Cells Mol. Endocrinol., February 1, 2005; 19(2): 312 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kato, M. Pinto, A. Carvajal, N. Espinoza, C. Monso, A. Sadarangani, M. Villalon, J. J. Brosens, J. O. White, J. K. Richer, et al. Progesterone Increases Tissue Factor Gene Expression, Procoagulant Activity, and Invasion in the Breast Cancer Cell Line ZR-75-1 J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1181 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Narayanan, A. A. Adigun, D. P. Edwards, and N. L. Weigel Cyclin-Dependent Kinase Activity Is Required for Progesterone Receptor Function: Novel Role for Cyclin A/Cdk2 as a Progesterone Receptor Coactivator Mol. Cell. Biol., January 1, 2005; 25(1): 264 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dai, L. Albitar, T. Nguyen, L. L. Laidler, M. Singh, and K. K. Leslie A therapeutic model for advanced endometrial cancer: Systemic progestin in combination with local adenoviral-mediated progesterone receptor expression Mol. Cancer Ther., January 1, 2005; 4(1): 169 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Berchuck, J. M. Schildkraut, R. M. Wenham, B. Calingaert, S. Ali, A. Henriott, S. Halabi, G. C. Rodriguez, D. Gertig, D. M. Purdie, et al. Progesterone Receptor Promoter +331A Polymorphism is Associated with a Reduced Risk of Endometrioid and Clear Cell Ovarian Cancers Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2141 - 2147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sumida, Y. Itahana, H. Hamakawa, and P.-Y. Desprez Reduction of Human Metastatic Breast Cancer Cell Aggressiveness on Introduction of Either Form A or B of the Progesterone Receptor and Then Treatment with Progestins Cancer Res., November 1, 2004; 64(21): 7886 - 7892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Ji, C. Aoyama, Y.-D. Nien, P. I. Liu, P. K. Chen, L. Chang, F. Z. Stanczyk, and A. Stolz Selective Loss of AKR1C1 and AKR1C2 in Breast Cancer and Their Potential Effect on Progesterone Signaling Cancer Res., October 15, 2004; 64(20): 7610 - 7617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Davies, D. Dai, D. M. Wolf, and K. K. Leslie Immunomodulatory and Transcriptional Effects of Progesterone Through Progesterone A and B Receptors in Hec50co Poorly Differentiated Endometrial Cancer Cells Reproductive Sciences, October 1, 2004; 11(7): 494 - 499. [Abstract] [PDF]
|
|
|
|
|
|
L. Cicatiello, R. Addeo, A. Sasso, L. Altucci, V. B. Petrizzi, R. Borgo, M. Cancemi, S. Caporali, S. Caristi, C. Scafoglio, et al. Estrogens and Progesterone Promote Persistent CCND1 Gene Activation during G1 by Inducing Transcriptional Derepres |
