Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene
Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene
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DOI：
10.1016/s0002-9440(10)63010-6
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发表时间：
2001-11-01
影响因子：
6
通讯作者：
Sers, C
中科院分区：
文献类型：
--
作者：
Kai, WC;Diatchenko, L;Sers, C
为了鉴定卵巢癌与正常卵巢中差异表达的新市场，我们将微阵列与来自正常人卵巢和晚期卵巢癌的cDNA杂交。该分析揭示了卵巢癌样本中caveolin-1基因（CAV 1）的下调。使用由来自不同匹配的人类肿瘤和正常组织的68个cDNA池组成的肿瘤组织军队证实了卵巢癌中CAV 1的抑制。免疫组化显示caveolin-1在正常和良性卵巢上皮细胞中表达，但在浆液性卵巢癌中表达缺失。在低级别癌中，小窝蛋白-1从正常上皮中观察到的膜相关模式重新分布到细胞质定位模式。未检测到caveolin-1的表达在四个卵巢癌细胞株研究。在SKOV-3和ES-2癌细胞，表达高水平的小窝蛋白-1蛋白，磷酸化的22 kd小窝蛋白-1亚型进行检测。分别使用5-氮杂-2 '脱氧胞苷和曲古抑菌素A抑制DNA甲基化和组蛋白去乙酰化，减轻了OAW 42和OVCAR-3细胞中小窝蛋白-1的下调，这部分是通过mRNA水平的直接调节介导的。CAV 1在卵巢癌细胞系OVCAR-3中的表达导致肿瘤细胞存活的抑制，表明CAV 1基因可能在人卵巢上皮中充当肿瘤抑制基因。
To identify novel markets differentially expressed in ovarian cancer versus normal ovary, we hybridized microarrays with cDNAs derived from normal human ovaries and advanced stage ovarian carcinomas. This analysis revealed down-regulation of the caveolin-1 gene (CAV1) in ovarian carcinoma samples. Suppression of CAV1 in ovarian carcinomas was confirmed using a tumor tissue army consisting of 68 cDNA pools from different matched human tumor and normal tissues. Immunohistochemistry demonstrated expression of caveolin-1 in normal and benign ovarian epithelial cells, but loss of expression in serous ovarian carcinomas. In low-grade carcinomas, redistribution of caveolin-1 from a membrane-associated pattern observed in normal epithelium to a cytoplasmic localization pattern was observed. No expression of caveolin-1 was detectable in four of six ovarian carcinoma cell lines investigated. In SKOV-3 and ES-2 carcinoma cells, which express high levels of the caveolin-1 protein, phosphorylation of the 22-kd caveolin-1 isoform was detected. Inhibition of both DNA methylation and histone deacetylation using 5-aza-2'deoxycytidine and Trichostatin A, respectively, relieves down-regulation of caveolin-1 in OAW42 and OVCAR-3 cells which is in part mediated by direct regulation at the mRNA level. Expression of CAV1 in the ovarian carcinoma cell line OVCAR-3, resulted in suppression of tumor cell survival in vitro, suggesting that the CAV1 gene is likely to act as a tumor suppressor gene in human ovarian epithelium.