Title

Immunomodulatory and transcriptional effects of progesterone through progesterone A and B receptors in Hec50co poorly differentiated endometrial cancer cells

Document Type

Article

Peer Reviewed

1

Publication Date

10-1-2004

NLM Title Abbreviation

J Soc Gynecol Investig

Journal/Book/Conference Title

Journal of the Society for Gynecologic Investigation

PubMed ID

15458748

DOI of Published Version

10.1016/j.jsgi.2004.04.003

Start Page

494

End Page

499

Abstract

OBJECTIVE: Derivatives of progesterone, progestins, are used to treat endometrial cancer; however, the pathways activated by the hormone have not been fully investigated. Progesterone acts through two receptor isoforms, progesterone receptors A and B (PRA and PRB), transcription factors that control the expression of downstream genes leading to endometrial differentiation. The purpose of this study was to perform an expression analysis to identify the mechanisms underlying progesterone's growth suppressive and immunomodulatory effects in endometrial cancer. METHODS: To study the molecular effects of progesterone, PRs were introduced into Hec50co cells. Expression array analyses followed by confirmatory semiquantitive reverse-transcriptase polymerase chain reaction (RT-PCR) experiments were performed. RESULTS: Expression analysis demonstrated a significant effect of progesterone after 12 hours of treatment on a number of genes, including cell signaling, DNA remodeling, apoptotic, tumor-suppressor, and transcription factors. Of particular interest was the consistent modulation of cytokines, which generally predicted for a powerful anti-inflammatory effect of progesterone through PR. Specifically, pro-inflammatory genes such as TNFalpha, IL-1beta, and MCP-1/MCAF-1 were down-regulated and anti-inflammatory genes such as TRAP1 and SMAD4 were induced. CONCLUSION: We have discovered that progesterone has a modulatory effect on inflammation and many other important cellular functions. These effects likely underlie the inhibitory effects of progesterone on tumor growth and invasion.

Keywords

Cytokines/genetics, Endometrial Neoplasms/immunology/metabolism, Female, Gene Expression Regulation/drug effects, Humans, Immunity/drug effects, Receptors, Progesterone/genetics/physiology, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic/drug effects, Transfection, Tumor Cells, Cultured

Published Article/Book Citation

Journal of the Society for Gynecologic Investigation (2004) 11:7, pp. 494-499.

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URL

https://ir.uiowa.edu/obgyn_pubs/29