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

细胞增殖的典型现象及其在妇科肿瘤激素调节中的控制。

基本信息

批准号：
13470351
负责人：
TAMAYA Teruhiko
金额：
$ 8.64万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

项目摘要

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.

该研究的结果如下。在妇科肿瘤细胞中，GnRH激活丝氨酸/苏氨酸磷酸酶2抑制细胞增殖，LPA通过与Gi连接的各个受体促进生长，提示不同Gi亚型的信号转导不同。雌激素受体(ER)α和ER相关受体(ERR)α/γ在早孕胎盘中的表达增加，提示胎盘通过这些受体具有生长潜力。随着子宫内膜癌的恶性进展，ERα的表达降低，而ERRα/γ的表达增加，提示ERR是一个不良的预后指标和治疗靶点。在子宫内膜癌细胞系(Ishikawa)中，磷酸化ERβ增加，而磷酸化ERα减少，提示PTEN在雌激素受体机制中的作用。植物雌激素(染料木素/染料木素和大豆素/大豆素)和氨苯乙胺作为一种抗雌激素作用，可降低IL-1α、肿瘤坏死因子-α和c-fos/jun的表达，从而降低小鼠子宫内膜癌的致癌性。菊泽泰和它的主要成分世茂藤具有抗雌激素和抗炎(COX-2抑制)的作用，有望成为癌症预防的候选药物。在妇科肿瘤细胞中，SHBG具有多态性和突变性，其剪接变异体的表达随着肿瘤的进展而增加。生长停滞特异性基因6(Gas6)是一种与SHBQ同源的结构，是Ax1/Sky家族磷酸化的配体，在雌激素依赖型、高分化的子宫内膜癌中表达。