Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression.
Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression.
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DOI：
10.3892/or.17.2.329
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发表时间：
2007-02
期刊：
影响因子：
4.2
通讯作者：
Masanori Miyanishi;M. Mandai;N. Matsumura;K. Yamaguchi;J. Hamanishi;T. Higuchi;K. Takakura;S. Fujii-S
中科院分区：
文献类型：
--
作者：
Masanori Miyanishi;M. Mandai;N. Matsumura;K. Yamaguchi;J. Hamanishi;T. Higuchi;K. Takakura;S. Fujii-S
恶性转化是由多步基因突变引起的，生长因子被认为在恶性表型的形成和维持中起重要作用。然而，没有直接的证据表明，一个特定的生长因子有助于恶性转化的表型正常的细胞。为了评估Acrogranin（也称为颗粒蛋白上皮前体; GEP）在卵巢癌发生中的功能，用hTERT、SV 40 LT和Acrogranin的组合基因转染被认为是原发性卵巢上皮癌起源的卵巢表面上皮（OSE）细胞。hTERT和SV 40 LT的引入足以使OSE细胞永生化，但不足以在裸鼠中形成肿瘤。相反，转染和过表达Acrogranin的永生化OSE细胞在软琼脂中表现出增强的克隆形成性和明显的裸鼠致瘤性。这是第一项研究表明，一种特定的生长因子在卵巢癌的恶性转化中起着直接的作用。
Malignant transformation is caused by multi-step genetic mutations, and growth factors are believed to play important roles in developing and maintaining malignant phenotype. However, there is no direct evidence that a specific growth factor contributes to malignant transformation of phenotypically normal cells. In order to assess the function of Acrogranin (also known as granulin epithelial precursor; GEP) in ovarian carcinogenesis, ovarian surface epithelial (OSE) cells, which are supposed to be the origin of primary ovarian epithelial cancer, were transfected with combined genes of hTERT, SV40 LT, and Acrogranin. Introduction of hTERT and SV40 LT was sufficient for immortalizing OSE cells but not enough for tumor formation in nude mice. In contrast, transfection and overexpression of Acrogranin in immortalized OSE cells showed augmented clonogenicity in soft agar and obvious tumorigenicity in nude mice. This is the first study showing evidence that a specific growth factor plays a direct role in malignant transformation in ovarian cancer development.