Studies on development and proliferation of endometrial cancer from sex steroid receptor and oncogenes

性类固醇受体与癌基因对子宫内膜癌发生、增殖的研究

• 批准号: 04404065
• 负责人: TAMAYA Teruhiko
• 金额: $ 8.32万
• 依托单位: GIFU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04404065/
• 关键词: Female Reproductive Organ; Corresponding Benign and Malignant Tumor; Corresponding Circumstance; Tumorigenesis and Proliferation; Sex Steroid Receptors; Oncogenes; Celluar SHBG; CBG; 婦人科腫瘍; マクロファージ; エストロゲン受容体; プロゲステロン受容体; 細胞内CBG; 細胞内SHBG; 子宮

In the tissues of female reproductive organs and corresponding benign and malignant tumors and circumstances, cellular profiferation and function are basically regulated by sex steroids, which imply the expressions (mRNA) of cellular oncogenes and steroid receptors, corresponding to mutations.(1) Synthesis of cellular SHBG/CBG (mRNA) in the uterine endometrium is primarily regulated by estrogen/progesterone. However abandance of SHBG gives the supply of estrogen to the endometriotic tissues.(2) Monocyte/macrophage in the ascites with pelvic endometriosis is activated, while expression of fms (M-CSF receptor) oncogene is stimulated by estrogen/progesterone, resulting in activation of tyrosine kinase, and anti-estrogenic compound inhites it.(3) Expressions of Ha-ras, c-myc, fos and jun oncogenes (mRNA) are induced by estrogen in the normal uterus but altered in corresponding benign and malignant tumors due to the difference of estrogen/progesterone effectiveness.(4) The cellular carcinogenesis and proliferation in endometrial cancer are partly related to estrogen action, which involves the pointmutations in the estrogen receptor domains and delations ofextracellular domains of erbB-1 and erbB-2 products, and overexpression of progesterone B type (proliferation) instead of A type (inhibition).Accumulation o those abnormalities of gene expressions might be related to the cancer events.

在女性生殖器官组织及相应的良、恶性肿瘤和环境中，细胞的增殖和功能基本上受性类固醇激素的调节，这意味着细胞癌基因和类固醇受体的表达（mRNA）与突变相对应。(1)子宫内膜中细胞SHBG/CBG（mRNA）的合成主要受雌激素/孕激素调节。然而，SHBG的缺乏为增生组织提供了雌激素的供应。(2)盆腔子宫内膜异位症腹水中的单核/巨噬细胞被激活，雌/孕激素刺激fms（M-CSF受体）癌基因表达，导致酪氨酸激酶激活，抗雌激素化合物可抑制其表达。(3)正常子宫组织中雌激素可诱导Ha-ras、c-myc、fos和jun癌基因（mRNA）的表达，而在相应的子宫良恶性肿瘤中，由于雌/孕激素效应的不同，其表达发生改变。(4)子宫内膜癌细胞的发生和增殖与雌激素作用有关，其中包括雌激素受体区域的点突变、erbB-1和erbB-2产物胞外区的缺失以及孕激素B型（增殖）而非A型（抑制）的过度表达，这些基因表达异常的积累可能与癌事件有关。

项目成果

Fujimoto,J.,et al.: "Expression of progesterone receptor form A and B mRNAs in gynecologic malignant tumors." Tumor Biology. 16. 339-346 (1995)

Fujimoto, J., et al.：“孕酮受体 A 型和 B 型 mRNA 在妇科恶性肿瘤中的表达”。

Tamaya T.,et al.: "Estrogen and androgen receptors in aorta of the rabbit and relulation by estrogen and androgen" Res.Commun.Chem.Pathol.Pharmacol.82. 3-11 (1993)

Tamaya T.,et al.：“兔子主动脉中的雌激素和雄激素受体以及雌激素和雄激素的关系”Res.Commun.Chem.Pathol.Pharmacol.82。

Misao R.,et al.: "Possible evidence for estrone specific binding sites in human uterine endometrial carcinoma" Obstet.Gynecol.Invest.(in press). (1994)

Misao R. 等人：“人类子宫内膜癌中雌酮特异性结合位点的可能证据”Obstet.Gynecol.Invest.（正在印刷中）。

Misao,R.,et al.: "Sex hormone-binding globulin mRNA levels in human uterine endometrium." Eur.J.Endocrinol.131. 623-629 (1994)

Misao,R.,et al.：“人子宫内膜中性激素结合球蛋白 mRNA 水平。”

Fujimoto,J.,et al.: "Tissue differnces in the expression of mRNAs of Ha-ras ,c-myc,fos and jun in human uterine endometrium,myometrium and leiomyoma under the influence of estrogen/progesterone." Tumor Biology. 15. 311-317 (1994)

Fujimoto, J., et al.：“雌激素/孕激素影响下人子宫内膜、子宫肌层和平滑肌瘤中 Ha-ras、c-myc、fos 和 jun mRNA 表达的组织差异”。