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Insulin-like Growth Factors in Ovarian Cancer and Their Effe...

Insulin-like Growth Factors in Ovarian Cancer and Their Effect on Progression

作     者:Herbert Yu Andrew Wiley Alicia Beeghly Dionyssios Katsaros 

作者单位:Yale University School of Medicine US University of TurinItaly Yale University School of Medicine US University of TurinItaly Yale University School of Medicine US University of TurinItaly Yale University School of Medicine US University of TurinItaly 

会议名称:《第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议》

会议日期:2006年

学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

摘      要:正Insulin - like growth factors (IGFs) are essential peptide hormones in regulation of cell proliferation, differentiation and apoptosis. As these cellular activities are critically related to tumorigenesis, IGFs are believed to play important roles in cancer development and progression. IGFs consist of two polypeptides, IGF - Ⅰ and IGF - Ⅱ , which bind to a specific cell membrane receptor with tyrosine kinase activity. Although the two peptides share extensive similarities in molecular structure and biologic action, these hormones are regulated differently and act at specific time. IGF - Ⅱ regulates cell proliferation and apoptosis during embryonic development and fetal growth, while IGF -Ⅰ exerts its actions in the postnatal life. Both IGF-Ⅰ and IGF - Ⅱ are subject to endocrine and paracrine regulation, and are expressed in ovarian tissue regulating its functions. Ovarian caner is one of the most fatal diseases for women and its etiology remains largely unknown. To evaluate IGF’s role in ovarian cancer, we investigated the effect and regulation of IGFs in ovarian cancer. The questions addressed in this study include a) which IGF, IGF-Ⅰ or IGF - Ⅱ , plays a more important role in ovarian cancer progression, b) whether IGF-Ⅰ genotype affects its phenotype in ovarian tissue, c) which IGF- Ⅱ promoters are more important for its expression in ovarian cancer, d) whether the promoter activity is affected by promoter methylation, and e) which laboratory methods are more reliable in assessing promoter methylation. We collected fresh frozen tumor tissue samples from 215 patients with primary epithelial ovarian cancer for the study. DNA, total RNA and cytosol proteins were extracted from the tissue samples and were analyzed for IGF-Ⅰ CA repeat polymorphism, IGF- Ⅱ promoter methylation, promoter- specific RNA expressions of IGF-Ⅰ and IGF - Ⅱ , as well as cytosol levels of IGF-Ⅰ, IGF- Ⅱ , and IGFBP - 3 proteins. The associations of these molecular markers with ovarian cancer

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