Choi Jung-Hye, Choi Kyung-Chul, Auersperg Nelly, Leung Peter C K
Department of Obstetrics and Gynecology, British Columbia Children's and Women's Hospital, British Columbia Research Institute for Children's and Women's Health, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5.
J Clin Endocrinol Metab. 2004 Nov;89(11):5508-16. doi: 10.1210/jc.2004-0044.
It has been previously demonstrated that human ovarian cancer cells express FSH receptor (FSHR). However, whether FSHR plays a role in ovarian cancer development is still ambiguous. To investigate the role of FSHR in tumor progression, we overexpressed the receptor in SV40 Tag immortalized ovarian surface epithelium (OSE) cell lines (IOSE-80PC, a postcrisis line, and IOSE-398), which are preneoplastic and nontumorigenic. We compared the expression levels of several selected oncogenes in nontransfected (80PC), vector-transfected (80PCV), FSHR-transfected IOSE (80PCF) cells, and established ovarian cancer cell lines (OVCAR-3 and SKOV-3). Significantly increased protein levels of epithelial growth factor receptor, HER-2/neu, and c-Myc, but not K-Ras, were observed in FSHR-overexpressing 80PCF cells when compared with 80PCV cells. Constitutive phosphorylation of ERK1/2 was augmented in 80PCF cells, whereas phosphorylation of the other MAPK including p38 and Jun N-terminal kinase was unchanged. Considerable constitutive phosphorylation of ERK1/2 was also observed in OVCAR-3 and SKOV-3 cell lines when compared with 80PCV. More importantly, 80PCF cells grew more rapidly than 80PC and 80PCV cells. In conclusion, we have demonstrated that FSHR was highly expressed in OVCAR-3 and 80PCF cells transfected with FSHR overexpression vector. The 80PCF cell line showed increased levels of epithelial growth factor receptor, HER-2/neu, and c-myc and constitutive activation of ERK1/2. The rate of proliferation of the 80PCF cells was increased, compared with control cell lines. These results suggest that the overexpression of FSHR may be associated with enhanced levels of potential oncogenic pathways and increased proliferation in preneoplastic ovarian surface epithelial cells.
先前已有研究表明，人卵巢癌细胞表达促卵泡激素受体（FSHR）。然而，FSHR在卵巢癌发展过程中是否发挥作用仍不明确。为了研究FSHR在肿瘤进展中的作用，我们在SV40 Tag永生化卵巢表面上皮（OSE）细胞系（IOSE - 80PC，一种危机后细胞系，以及IOSE - 398）中过表达该受体，这些细胞系为肿瘤前体细胞系且无致瘤性。我们比较了未转染（80PC）、载体转染（80PCV）、FSHR转染的IOSE细胞（80PCF）以及已建立的卵巢癌细胞系（OVCAR - 3和SKOV - 3）中几种选定癌基因的表达水平。与80PCV细胞相比，在FSHR过表达的80PCF细胞中观察到上皮生长因子受体、HER - 2/neu和c - Myc的蛋白水平显著升高，但K - Ras的蛋白水平未升高。80PCF细胞中ERK1/2的组成型磷酸化增强，而包括p38和Jun N末端激酶在内的其他丝裂原活化蛋白激酶（MAPK）的磷酸化未发生变化。与80PCV相比，在OVCAR - 3和SKOV - 3细胞系中也观察到ERK1/2有相当程度的组成型磷酸化。更重要的是，80PCF细胞比80PC和80PCV细胞生长得更快。总之，我们已证明FSHR在OVCAR - 3和用FSHR过表达载体转染的80PCF细胞中高表达。80PCF细胞系显示上皮生长因子受体、HER - 2/neu和c - myc水平升高以及ERK1/2的组成型激活。与对照细胞系相比，80PCF细胞的增殖速率增加。这些结果表明，FSHR的过表达可能与肿瘤前卵巢表面上皮细胞中潜在致癌途径水平的增强和增殖增加有关。
