NCBI Summary:
TCF2 encodes transcription factor 2, a liver-specific factor of the homeobox-containing basic helix-turn-helix family. The TCF2 protein is believed to form heterodimers with another liver-specific member of this transcription factor family, TCF1; depending on the TCF2 isoform, the result may be to activate or inhibit transcription of target genes. Mutation of TCF2 that disrupts normal function has been identified as the cause of MODY5 (Maturity-Onset of Diabetes, Type 5). A third human transcript variant is believed to exist based on such a variant in the rat: however, to date such an mRNA species has not been isolated.
General function
DNA binding, Transcription factor
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Cellular localization
Nuclear
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Ovarian function
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Expression regulated by
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Ovarian localization
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Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1beta as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma.
Tsuchiya A, et al .
Of all of the epithelial ovarian cancers, clear cell carcinoma (CCC) of the ovary has the worst prognosis. We applied the oligonucleotide array technique to identify genes generally involved in CCC. Of the approximately 12,600 genes that were analyzed, 28 were expressed significantly differently between four CCC and seven non-CCC cell lines. Among 16 up-regulated genes in CCC, we further investigated a transcription factor, hepatocyte nuclear factor-1beta (HNF-1beta). We validated up-regulation of HNF-1beta in CCC in terms of both mRNA and protein level using real-time quantitative reverse transcriptase-polymerase chain reaction and immunoblotting. Immunohistochemical analysis of 83 surgically resected ovarian cancers showed that almost all CCC specimens (21 of 22 cases) had nuclear staining for HNF-1beta, whereas most non-CCC specimens (60 of 61 cases) showed no immunostaining or only focal and faint staining in the nucleus. Furthermore, we investigated the significance of HNF-1beta expression in CCC using RNA interference. The reduction of HNF-1beta expression by RNA interference induced apoptotic cell death in ovarian CCC cells, which was confirmed by terminal dUTP nick-end labeling and fluorescence-activated cell-sorting analyses. Our results suggest that HNF-1beta is not only an excellent CCC-specific molecular marker but also a molecular target for therapy of ovarian CCC.