This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Sartorius, C. A. Articles by Horwitz, K. B. Search for Related Content PubMed PubMed Citation Articles by Sartorius, C. A. Articles by Horwitz, K. B.

Progestins Initiate a Luminal to Myoepithelial Switch in Estrogen-Dependent Human Breast Tumors without Altering Growth

¹ Division of Endocrinology, Department of Medicine and ² Department of Pathology, University of Colorado Health Sciences Center, Aurora, Colorado

Requests for reprints: Carol A. Sartorius, Division of Endocrinology, Department of Medicine, University of Colorado Health Sciences Center, 12801 East 17th Avenue MS8106, Aurora, CO 80045-7163. Phone: 303-724-3941; Fax: 303-724-3920; E-mail: Carol.Sartorius{at}uchsc.edu.

Although long-term clinical use of progestins is associated with an increased incidence of breast cancers, their role in established cancers is unclear. Estrogens are considered to be the main mitogens in the majority of breast cancers. Whether progesterone affects proliferation and/or differentiation is under debate. To assess the role of progesterone in established breast cancers, we used T47D human breast cancer cells that are estrogen receptor (ER) positive and either progesterone receptor (PR) negative or positive for PRA, PRB, or both. These cells were grown as strictly estrogen-dependent solid tumors in ovariectomized female nude mice. Progesterone or medroxyprogesterone acetate (MPA) alone did not support tumor growth, nor did progesterone or MPA given simultaneously with estrogen significantly alter estrogen-dependent tumor growth. However, treatment of mice bearing ER+PR+ but not ER+PR– tumors with either progesterone or MPA increased expression of the myoepithelial cytokeratins (CK) 5 and 6 in a subpopulation of tumor cells. These CK5+/CK6+ cells had decreased expression of luminal epithelial CK8, CK18, and CK19. We conclude that progestins exert differentiative effects on tumors characterized by transition of a cell subpopulation from luminal to myoepithelial. This may not be beneficial, however, because such a phenotype is associated with poor prognosis.

This article has been cited by other articles:

				K. B. Horwitz Commentary: The Year in Basic Science: Update of Estrogen Plus Progestin Therapy for Menopausal Hormone Replacement Implicating Stem Cells in the Increased Breast Cancer Risk Mol. Endocrinol., December 1, 2008; 22(12): 2743 - 2750. [Abstract] [Full Text] [PDF]

				K. B. Horwitz and C. A. Sartorius Progestins in Hormone Replacement Therapies Reactivate Cancer Stem Cells in Women with Preexisting Breast Cancers: A Hypothesis J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3295 - 3298. [Abstract] [Full Text] [PDF]

				K. B. Horwitz, W. W. Dye, J. C. Harrell, P. Kabos, and C. A. Sartorius Rare steroid receptor-negative basal-like tumorigenic cells in luminal subtype human breast cancer xenografts PNAS, April 15, 2008; 105(15): 5774 - 5779. [Abstract] [Full Text] [PDF]

				Y. Liang, C. Besch-Williford, R. A. Brekken, and S. M. Hyder Progestin-Dependent Progression of Human Breast Tumor Xenografts: A Novel Model for Evaluating Antitumor Therapeutics Cancer Res., October 15, 2007; 67(20): 9929 - 9936. [Abstract] [Full Text] [PDF]

				A. Kariagina, M. D. Aupperlee, and S. Z. Haslam Progesterone Receptor Isoforms and Proliferation in the Rat Mammary Gland during Development Endocrinology, June 1, 2007; 148(6): 2723 - 2736. [Abstract] [Full Text] [PDF]

				B. M. Jacobsen, J. C. Harrell, P. Jedlicka, V. F. Borges, M. Varella-Garcia, and K. B. Horwitz Spontaneous Fusion with, and Transformation of Mouse Stroma by, Malignant Human Breast Cancer Epithelium Cancer Res., August 15, 2006; 66(16): 8274 - 8279. [Abstract] [Full Text] [PDF]

				D. M. E. Harvell, J. K. Richer, D. C. Allred, C. A. Sartorius, and K. B. Horwitz Estradiol Regulates Different Genes in Human Breast Tumor Xenografts Compared with the Identical Cells in Culture Endocrinology, February 1, 2006; 147(2): 700 - 713. [Abstract] [Full Text] [PDF]