Tilocca, Pier Luigi (2013) Ruolo del gene YAP e della via YAP/CTGF nel corso della cancerogenesi epatica nel ratto e nell'uomo. Doctoral Thesis.
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Aim: YAP is a small protein that binds to many transcription factors and modulates their activity. The regulation of YAP activity is not well understood. CTGF is one of target genes of YAP. The aim of this study is to detect YAP/CTGF pathway activation through measuring gene expression and protein levels in samples of rat liver.
In this study we assessed the role of YAP/CTGF pathway during hepatocarcinogenesis in susceptible Fisher F344 (F344) and resistant Brown Norway (BN) rats.
Methods: Preneoplastic liver (4 weeks after initiation), early low-grade dysplastic nodules (12 weeks), dysplastic nodules (mostly low-grade in BN and high-grade dyplastic in F344 rats; 32 weeks) and HCCs (57-60 weeks) were induced in F344 and BN rats according to the resistant hepatocyte protocol.
Levels of CTGF and YAP protein and RNA, were determined by Western Blotting and Real-Time–RT PCR analyses in rat samples.
Results: The results, obtained in the weeks after treatment, generally show an increase of both YAP and CTGF in F344 strains compared to BN rats. In details the difference for YAP expression was more marked in IV and XII week. On the other hand, CTGF expression, after a substantial equivalence in IV week, was always higher in F344 than in BN. Moreover YAP and CTGF expression was higher in HCCs than in normal liver in both strains.
Conclusion: Overexpression of YAP/CTGF pathway seems to be associated with progression of liver carcinogenesis, with maximum expression in HCCs nodules. This seems to reveal an important role of this pathway in liver cancer biology.
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