HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kester, H. A. Articles by van der Burg, B. Search for Related Content PubMed PubMed Citation Articles by Kester, H. A. Articles by van der Burg, B. Social Bookmarking                      What's this?

Volume 272, Number 26, Issue of June 27, 1997 pp. 16637-16643
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Novel Progesterone Target Genes Identified by an Improved Differential Display Technique Suggest That Progestin-induced Growth Inhibition of Breast Cancer Cells Coincides with Enhancement of Differentiation

(Received for publication, December 12, 1996, and in revised form, April 14, 1997)

From the Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands

Progesterone is an important regulator of normal and malignant breast epithelial cells. In addition to stimulating development of normal mammary epithelium, it can be used to treat hormone-dependent breast tumors. However, the mechanism of growth inhibition by progestins is poorly understood, and only a limited number of progesterone target genes are known so far. We therefore decided to clone such target genes by means of differential display polymerase chain reaction. In this paper, we describe an improved differential display strategy that eliminates false positives, along with the identification of nine positive (TSC-22, CD-9, Na⁺/K⁺-ATPase 1, desmoplakin, CD-59, FKBP51, and three unknown genes) and one negative progesterone target genes (annexin-VI) from the mammary carcinoma cell line T47D, which is growth-inhibited by progestins. None of these genes have been reported before to be progesterone targets. Regulation of desmoplakin, CD-9, CD-59, Na⁺/K⁺-ATPase 1, and annexin-VI by the progestin suggests that progesterone induces T47D cells to differentiate. Three of these genes were repressed by estradiol and up-regulated by the progestin. Estradiol treatment of T47D cells also leads to formation of lamellipodia and delocalization of two cell adhesion proteins, E-cadherin and -catenin. All these effects were reversed by the progestin. These data suggest that estradiol dedifferentiates T47D cells, while progestins have the opposite effect. This may be linked to the capacity of progestins to inhibit tumor growth.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Gava, C. L. Clarke, C. Bye, K. Byth, and A. deFazio Global gene expression profiles of ovarian surface epithelial cells in vivo J. Mol. Endocrinol., June 1, 2008; 40(6): 281 - 296. [Abstract] [Full Text] [PDF]

				T. Suzuki, F. Schirra, S. M. Richards, R. V. Jensen, and D. A. Sullivan Estrogen and Progesterone Control of Gene Expression in the Mouse Meibomian Gland Invest. Ophthalmol. Vis. Sci., May 1, 2008; 49(5): 1797 - 1808. [Abstract] [Full Text] [PDF]

				X. Wu, M. Yamada-Mabuchi, E. J. Morris, P. S. Tanwar, L. Dobens, S. Gluderer, S. Khan, J. Cao, H. Stocker, E. Hafen, et al. The Drosophila homolog of human tumor suppressor TSC-22 promotes cellular growth, proliferation, and survival PNAS, April 8, 2008; 105(14): 5414 - 5419. [Abstract] [Full Text] [PDF]

				M. B. Cox, D. L. Riggs, M. Hessling, F. Schumacher, J. Buchner, and D. F. Smith FK506-Binding Protein 52 Phosphorylation: A Potential Mechanism for Regulating Steroid Hormone Receptor Activity Mol. Endocrinol., December 1, 2007; 21(12): 2956 - 2967. [Abstract] [Full Text] [PDF]

				M. Iida, C. H. Anna, N. D. Gaskin, N. J. Walker, and T. R. Devereux The Putative Tumor Suppressor Tsc-22 is Downregulated Early in Chemically Induced Hepatocarcinogenesis and may be a Suppressor of Gadd45b Toxicol. Sci., September 1, 2007; 99(1): 43 - 50. [Abstract] [Full Text] [PDF]

				F. Gizard, R. Robillard, B. Gross, O. Barbier, F. Revillion, J.-P. Peyrat, G. Torpier, D. W. Hum, and B. Staels TReP-132 Is a Novel Progesterone Receptor Coactivator Required for the Inhibition of Breast Cancer Cell Growth and Enhancement of Differentiation by Progesterone. Mol. Cell. Biol., October 1, 2006; 26(20): 7632 - 7644. [Abstract] [Full Text] [PDF]

				T. Daikoku, S. Tranguch, D. B. Friedman, S. K. Das, D. F. Smith, and S. K. Dey Proteomic Analysis Identifies Immunophilin FK506 Binding Protein 4 (FKBP52) as a Downstream Target of Hoxa10 in the Periimplantation Mouse Uterus Mol. Endocrinol., March 1, 2005; 19(3): 683 - 697. [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]

				C. Qi, P. Kashireddy, Y. T. Zhu, S. M. Rao, and Y.-J. Zhu Null Mutation of Peroxisome Proliferator-activated Receptor-interacting Protein in Mammary Glands Causes Defective Mammopoiesis J. Biol. Chem., August 6, 2004; 279(32): 33696 - 33701. [Abstract] [Full Text] [PDF]

				X. Li and B. W. O'Malley Unfolding the Action of Progesterone Receptors J. Biol. Chem., October 10, 2003; 278(41): 39261 - 39264. [Full Text] [PDF]

				S. Oesterreich, W. Deng, S. Jiang, X. Cui, M. Ivanova, R. Schiff, K. Kang, D. L. Hadsell, J. Behrens, and A. V. Lee Estrogen-mediated Down-Regulation of E-cadherin in Breast Cancer Cells Cancer Res., September 1, 2003; 63(17): 5203 - 5208. [Abstract] [Full Text] [PDF]

				T. R. Hubler, W. B. Denny, D. L. Valentine, J. Cheung-Flynn, D. F. Smith, and J. G. Scammell The FK506-Binding Immunophilin FKBP51 Is Transcriptionally Regulated by Progestin and Attenuates Progestin Responsiveness Endocrinology, June 1, 2003; 144(6): 2380 - 2387. [Abstract] [Full Text] [PDF]

				V. C.-L. Lin, R. Jin, P.-H. Tan, S.-E. Aw, C.-T. Woon, and B.-H. Bay Progesterone Induces Cellular Differentiation in MDA-MB-231 Breast Cancer Cells Transfected with Progesterone Receptor Complementary DNA Am. J. Pathol., June 1, 2003; 162(6): 1781 - 1787. [Abstract] [Full Text] [PDF]

				C. Orelio and E. Dzierzak Identification of 2 novel genes developmentally regulated in the mouse aorta-gonad-mesonephros region Blood, March 15, 2003; 101(6): 2246 - 2249. [Abstract] [Full Text] [PDF]

				C. R. Sinars, J. Cheung-Flynn, R. A. Rimerman, J. G. Scammell, D. F. Smith, and J. Clardy Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes PNAS, February 4, 2003; 100(3): 868 - 873. [Abstract] [Full Text] [PDF]

				H. Vermeer, B. I. Hendriks-Stegeman, B. van der Burg, S. C. van Buul-Offers, and M. Jansen Glucocorticoid-Induced Increase in Lymphocytic FKBP51 Messenger Ribonucleic Acid Expression: A Potential Marker for Glucocorticoid Sensitivity, Potency, and Bioavailability J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 277 - 284. [Abstract] [Full Text] [PDF]

				E. Smid-Koopman, L. J. Blok, L. C. M. Kuhne,, C. W. Burger, T. J. M. Helmerhorst, A. O. Brinkman, and F. J. Huikeshoven Distinct Functional Differences of Human Progesterone Receptors A and B on Gene Expression and Growth Regulation in Two Endometrial Carcinoma Cell Lines Reproductive Sciences, January 1, 2003; 10(1): 49 - 57. [Abstract] [PDF]

				V. C.-L. Lin, E. H. Ng, S. E. Aw, M. G.-K. Tan, E. H.-L. Ng, and B. H. Bay Progesterone Induces Focal Adhesion in Breast Cancer Cells MDA-MB-231 Transfected with Progesterone Receptor Complementary DNA Mol. Endocrinol., March 1, 2000; 14(3): 348 - 358. [Abstract] [Full Text]

				R. M. Korah, V. Sysounthone, Y. Golowa, and R. Wieder Basic Fibroblast Growth Factor Confers a Less Malignant Phenotype in MDA-MB-231 Human Breast Cancer Cells Cancer Res., February 1, 2000; 60(3): 733 - 740. [Abstract] [Full Text]

				H. A. Kester, C. Blanchetot, J. den Hertog, P. T. van der Saag, and B. van der Burg Transforming Growth Factor-beta -stimulated Clone-22 Is a Member of a Family of Leucine Zipper Proteins That Can Homo- and Heterodimerize and Has Transcriptional Repressor Activity J. Biol. Chem., September 24, 1999; 274(39): 27439 - 27447. [Abstract] [Full Text] [PDF]

				L. Vaßen, W. Wegrzyn, and L. Klein-Hitpass Human Insulin Receptor Substrate-2 (IRS-2) Is a Primary Progesterone Response Gene Mol. Endocrinol., March 1, 1999; 13(3): 485 - 494. [Abstract] [Full Text]