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Genetic and epigenetic alterations of steroidogenic factor-1 in ovarian tumors
Steroidogenic factor-1 (SF-1), the product of the NR5A1 gene, is an essential transcription factor that is known to regulate steroidogenesis in ovarian epithelia, including the synthesis of progesterone, a suppressor of ovarian cancer. Expression of the SF-1 protein, a potential ovarian tumor suppre...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583749/ https://www.ncbi.nlm.nih.gov/pubmed/23291911 http://dx.doi.org/10.3892/ijo.2012.1758 |
Sumario: | Steroidogenic factor-1 (SF-1), the product of the NR5A1 gene, is an essential transcription factor that is known to regulate steroidogenesis in ovarian epithelia, including the synthesis of progesterone, a suppressor of ovarian cancer. Expression of the SF-1 protein, a potential ovarian tumor suppressor, has been demonstrated in normal OSE cells, but is lost in most ovarian tumors and ovarian tumor cell lines. We examined loss of heterozygosity (LOH) and promoter methylation as potential mechanisms that may explain the loss of SF-1 protein in ovarian tumor tissues. Genotyping of three NR5A1 SNPs in matched tumor/normal tissues identified LOH in 16/36 (44%) of the ovarian tumors successfully analyzed, and somatic mutations (gain of allele) in 10% of the tumors. Furthermore, a methylation-sensitive restriction enzyme method was used to demonstrate statistically significant (p<0.0001) increase in the frequency of NR5A1 gene methylation in ovarian tumors (36/46; 78%) versus normal ovaries (1/11; 9%). These data suggest that the SF-1 encoding gene exhibits frequent genetic (LOH/base substitution) and epigenetic (methylation) somatic alterations in ovarian tumors. These data also present novel molecular mechanisms that may explain the loss of SF-1 protein in ovarian tumors, and its potential role in ovarian carcinogenesis. |
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