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Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. Litman, E. Schonteich, Kimberly Leslie
Progesterone Regulation Of Activating Protein-1 Transcriptional Activity: A Possible Mechanism Of Progesterone Inhibition Of Endometrial Cancer Cell Growth, Donghai Dai, E. Litman, E. Schonteich, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium and cancers derived from it are classic models of hormone action: estrogen promotes growth and progesterone inhibits proliferation and results in differentiation. We have now identified a major pathway through which progesterone causes these growth-limiting effects. Ligand-bound progesterone receptors modulate the composition and transcriptional activity of members of the activating protein-1 (AP-1) family, and in particular, c-Jun. First, a dominant negative form of c-Jun inhibits the constitutive growth of Hec50co cells in a manner similar to the effects of progesterone through progesterone B receptors. Second, progesterone inhibits the transcriptional activity of the AP-1 complex in reporter gene …
Gene Regulation Profiles By Progesterone And Dexamethasone In Human Endometrial Cancer Ishikawa H Cells, S. Davies, Donghai Dai, G. Pickett, Kimberly Leslie
Gene Regulation Profiles By Progesterone And Dexamethasone In Human Endometrial Cancer Ishikawa H Cells, S. Davies, Donghai Dai, G. Pickett, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Progesterone and glucocorticoids such as dexamethasone mediate distinct biological functions, yet they bind to receptors that recognize the same consensus DNA response element. In breast cancer, progestins are associated with the incidence and progression of tumors, whereas glucocorticoids are growth-suppressive in mammary cancer cells; the differential effects of these two steroids are less well understood in the hormone-dependent disease cancer of the uterine endometrium. We set out to identify genes that are regulated by progesterone through progesterone receptors and dexamethasone through glucocorticoid receptors in a well-differentiated human endometrial cancer cell line. METHODS: PR- and GR-positive Ishikawa H endometrial cancer …
Identification Of A Novel Mechanism Of Nf-Kappab Inactivation By Progesterone Through Progesterone Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells: Induction Of A20 And Abin-2, S. Davies, Donghai Dai, I. Feldman, G. Pickett, Kimberly Leslie
Identification Of A Novel Mechanism Of Nf-Kappab Inactivation By Progesterone Through Progesterone Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells: Induction Of A20 And Abin-2, S. Davies, Donghai Dai, I. Feldman, G. Pickett, Kimberly Leslie
Kimberly K. Leslie
OBJECTIVE: Nuclear factor kappa B (NFkappaB) is a strong anti-apoptotic factor, which is constitutively active in human endometrial cancer cells. Progesterone is the principal growth inhibitory hormone in the endometrial epithelium and promotes apoptosis. To identify the pathways through which progesterone controls NFkappaB function, we explored its genomic and non-genomic effects in endometrial cancer cells. METHODS: PR-negative Hec50co endometrial cancer cells were engineered to express high levels of the A or B isoform of PR (PRA or PRB) by adenoviral infection. Cells were treated with progesterone or vehicle alone, and RNA was isolated. Affymetrix microarrays were performed and transcriptional control …
Progesterone Inhibits Human Endometrial Cancer Cell Growth And Invasiveness: Down-Regulation Of Cellular Adhesion Molecules Through Progesterone B Receptors, Donghai Dai, D. Wolf, E. Litman, M. White, Kimberly Leslie
Progesterone Inhibits Human Endometrial Cancer Cell Growth And Invasiveness: Down-Regulation Of Cellular Adhesion Molecules Through Progesterone B Receptors, Donghai Dai, D. Wolf, E. Litman, M. White, Kimberly Leslie
Kimberly K. Leslie
Progesterone is a critical steroid hormone that controls cell proliferation and differentiation in the female reproductive tract. Progesterone acts through two nuclear receptor isoforms, progesterone receptors A and B (PRA and PRB, respectively), each with unique cellular effects. Loss of PRB has recently been linked to the development of poorly differentiated endometrial tumors, a lethal form of cancer. To study the molecular effects of progesterone, progesterone receptors were introduced into Hec50co endometrial cancer cells by adenoviral vectors encoding either PRA or PRB. Progesterone induced the cyclin-dependent kinase inhibitors p21 and p27, thereby significantly reducing the percentage of proliferating cells. Cancer …