Expression and anti-proliferative effect of a second form of gonadotropin-releasing hormone in normal and neoplastic ovarian surface epithelial cells

Expression and anti-proliferative effect of a second form of gonadotropin-releasing hormone in normal and neoplastic ovarian surface epithelial cells
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DOI:
10.1210/jc.86.10.5075
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发表时间:
2001-10-01
影响因子:
5.8
通讯作者:
Leung, PCK
Leung, PCK
中科院分区:
医学2区
文献类型:
--
作者:
Choi, KC;Auersperg, N;Leung, PCK

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上皮性卵巢癌是妇科恶性肿瘤最常见的致死原因,它似乎起源于卵巢表面上皮(OSE),但卵巢肿瘤发生的确切机制尚未阐明。最近已有报道在包括卵巢在内的各种人类组织中克隆了第二种形式的促性腺激素释放激素(GnRH-II)。然而,GnRH-II在OSE和卵巢癌中的表达和作用尚不清楚。在本研究中,除GnRH受体(GnRH-R)外,GnRH-II在正常OSE、永生化OSE(IOSE)细胞、卵巢肿瘤原代培养细胞和卵巢癌细胞系中均有表达。随着GnRH-I和GnRH-II剂量的增加(10(-9)-10(-7)M),对非致瘤性Iose-29和致瘤性Iose-29EC细胞均有生长抑制作用。这些结果首次表明GnRH-II的表达和潜在的抗增殖作用,提示GnRH-II与GnRH-I类似,可能在正常和肿瘤OSE细胞中具有生长调节作用。
Epithelial ovarian carcinomas are the most common cause of death from gynecological malignancies and appear to arise from ovarian surface epithelium (OSE), but the exact mechanism of ovarian tumorigenesis has not been elucidated. Recent cloning of a second form of gonadotropin-releasing hormone (GnRH-II) has been reported in various human tissues including the ovary. However, the expression and role of GnRH-II in human OSE and ovarian carcinomas is not known. In the present study, we demonstrated that in addition to the GnRH receptor (GnRH-R), GnRH-II mRNA is expressed in normal OSE, immortalized OSE (IOSE) cells, primary cultures of ovarian tumors and ovarian cancer cell lines. Treatments with increasing doses (10(-9) - 10(-7) M) of GnRH-I and -II resulted in a growth-inhibition in both non-tumorigenic IOSE-29 and tumorigenic IOSE-29EC cells. These results indicate for the first time the expression and potential anti-proliferative effect of GnRH-II, suggesting that GnRH-II, similar to GnRH-I, may have a growth-regulatory effect in normal and neoplastic OSE cells.