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Alternative gonadotropin-releasing hormone I and II processing products secreted from endometrial carcinoma

子宫内膜癌分泌的替代性促性腺激素释放激素 I 和 II 加工产品

基本信息

批准号：
12470340
负责人：
IMAI Atsushi
金额：
$ 3.2万
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：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470340/
关键词：
Endometrial cancer Apoptosis Ser Thr phosphatase GnRH II GnRH GnRH receptor ProGnRH II リゾポスファチジン酸 (1-5)GnRH 卵巣癌酵素の細胞内再分布エンドペプチダーゼプロセッシング異常プレGnRH ウエスタンブロッティング

项目摘要

Gonadotropin-releasing hormone (GnRH) receptor is demonstrated in uterine endometrial carcinoma. The endometrial carcinoma also produces GnRH or -like peptide, which prompted us to examine whether the intratumoral 'GnRH' serves as natural ligand for its receptor. Endometrial carcinomas surgically removed had been screened for GnRH receptor expression before analysis. The 'GnRH' in endometrial carcinoma cell-enriched culture media was characterized by immunoblots in tricine-supplied electrophoresis system and subsequent amino acid sequencing. Three major proteins of 10.0kDa,7.6kDa and 1.1kDa corresponding to pre-proGnRH, proGnRH and decapeptide GnRH, respectively, were detected in all of ten endometrial carcinoma specimens tested. Immunoreactive 'GnRH' contents in the culture media, assessed by RIA, ranged from 0.08 to 0.1nM. In chorionic cells-conditioned media, only 1.1-kDa protein was detected. Endometrial carcinoma cells secrete alternative GnRH processing products in addition to natural GnRH. The GnRH variants may compete with mature GnRH at the level of its receptors, perhaps counteracting GnRH signaling pathway to retard cell proliferation.

促性腺激素释放激素（GnRH）受体在子宫内膜癌中被证实。子宫内膜癌也产生GnRH或类似肽，这促使我们研究肿瘤内的“GnRH”是否作为其受体的天然配体。在分析之前，已对手术切除的子宫内膜癌进行了GnRH受体表达筛查。子宫内膜癌细胞富集培养基中的“GnRH”的特征在于在三羟甲基甘氨酸提供的电泳系统中的免疫印迹和随后的氨基酸测序。10例子宫内膜癌组织中均检测到前促性腺激素释放激素原（pre-proGnRH）、促性腺激素释放激素原（proGnRH）和十肽促性腺激素释放激素（GnRH）三种主要蛋白，其分子量分别为10.0kDa、7.6kDa和1.1kDa。通过RIA评估，培养基中的免疫反应性“GnRH”含量范围为0.08至0.1nM。在绒毛膜细胞条件培养基中，仅检测到1.1-kDa蛋白。子宫内膜癌细胞除了分泌天然GnRH外，还分泌替代性GnRH加工产物。GnRH变体可能在其受体水平上与成熟GnRH竞争，可能抵消GnRH信号通路以延缓细胞增殖。