Immunomodulatory and Transcriptional Effects of Progesterone Through Progesterone A and B Receptors in Hec5Oco Poorly Differentiated Endometrial Cancer Cells
Tóm tắt
Derivatives ofprogesterone, progestins, are used to treat endometrial cancer; however, the pathways activated by the hormone have not beenfully 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 immuno-modulatory effects in endometrial cancer. 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. Expression analysis demonstrated a significant effect ofprogesterone 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 predictedfor a powerfil anti-inflammatory effect ofprogesterone through PR. Specifically, pro-inflammatory genes such as TNFα, IL-1β, and MCP-1/MCAF-1 were down-regulated and anti-inflammatory genes such as TRAPi and SMAD4 were induced. We have discovered that progesterone has a modulatory effect on inflammation and many other important cellularfunctions. These effects likely underlie the inhibitory effects ofprogesterone on tumor growth and invasion.
Tài liệu tham khảo
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