Mecliamisms of cellelar proliferation and its control in hormonal regulation of gynecological tumors.

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The results of the titled study are as follows. In the gynecological tumor cells, GnRH activates serine/threonime phosphatase type2 for proliferative inhibition and LPA increases those growth via Gi-linked each receptor, suggesting the different signaling in different Gi subtypes. Expressions of estrogen receptor (ER) α and ER-related receptor (ERR) α/γ increase in human placentas during the early pregnancy, suggesting the growth potential of placenta by those receptors. As the malignant advance in the endometrial cancers, expression of ER α decreases, yet ERR α/γ increase, suggesting ERR is a poor prognostic indicator and a therapeutic target. In endometrial PTEN-introduced cancer cell line (Ishikawa), phosphorylated ERβ increases, yet phosphorylated ER α decreases, suggesting the effect of PTEN on estrogen receptor mechanism. Phytoestrogens (genistin/genistein and daizin/daidzen)and tremiphen as a SERM decrease the expressions of IL-1α, TNF-α, and c-fos/jun, resulting in decreased carcinogenesis in mouse endometrial carcinomas as an anti-estrogeic effect. Juzentaiho-to and its main component (Shimotu-to) decrease this carcinogenesis, with anti-estrogenic and anti-inflammatory (COX-2 inhibition) effects and will be the candidates of cancer prophylaxis. In gynecological cancer cells, SHBG has polymorphisms and mutations, and its splicing variant expression increases as the malignant advance. Growth arrest-specific gene6 (gas6), a homologic structure with SHBQ is a ligand of Axl/Sky family with phosphorylation, and is expressed in the estrogen-dependent, well differentiated endometrial cancers.