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Journal of the Society for Gynecologic Investigation
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Distinct Functional Differences of Human Progesterone Receptors A and B on Gene Expression and Growth Regulation in Two Endometrial Carcinoma Cell Lines

Ellen Smid-Koopman, MD, PhD

Department of Obstetrics and Gynecology, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands esmidkoopman{at}hotmail.com

Leen J. Blok, PhD

Liesbeth C. M. Kühne,, BSc

Curt W. Burger, MD, PhD

Thoe J. M. Helmerhorst, MD, PhD

Albert O. Brinkman, PhD

Frans J. Huikeshoven, MD, PhD

Departments of Obstetrics and Gynaecology, and Reproduction and Development, Erasmus Medical Center, Rotterdam, The Netherlands

Objective: To study the functional differences between the two progesterone receptor isoforms (hPRA and hPRB) in human endometrial cancer, two new endometrial carcinoma cell lines were created—one expressing hPRA and one expressing hPRB.

Methods: A well-differentiated, hPR-negative Ishikawa cell line was stably transfected with either hPRA or hPRB cDNA. Transfected cells were selected, and two cell lines expressing approximately equal amounts of receptor were isolated—one expressing hPRA (PRA-14) and one expressing hPRB (PRB-59).

Results: Cell growth experiments revealed a growth-inhibitory response to progestins (MPA and R5020) in the PRB-59 cells but not in the PRA-14 cells. Differences in expression of genes targeted by the two isoforms were studied using a cDNA expression array technique. A different se to genes appeared to be progesterone regulated in the PRA-14 cells than in the PRB-59 cells. None of the genes were regulated by both hPRA and hPRB. Insulin-like growth factor binding protein 3 expression was studied in more detail as an example of a gene regulated in PRB-59 cells but not in PRA-14 cells.

Conclusion: We established a new model to study functional differences between the two hPR isoforms in human endometrial carcinoma cells. This model revealed distinctive differences in target gene regulation between the two hPR isoforms. Moreover, antiproliferative actions of progesterone on human endometrial cancer cells could be observed only in the PRB-expressing cell line.

Key Words: hPRA • hPRB • cDNA expression array • genes • endometrial cancer

Journal of the Society for Gynecologic Investigation, Vol. 10, No. 1, 49-57 (2003)
DOI: 10.1177/107155760301000110
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