Role of expression of FIP200 protein in progression of hepatocellular carcinoma

Abstract

e22147 Background: FIP200 protein is a newly identified protein, and recent report has shown that FIP200 interacts with p53 and inhibit progression and proliferation. Although expression of FIP200 has been confirmed in normal liver,the expression and function in human HCC is completely unknown. In this study, we examined expression of FIP200 in HCC cell lines and investigated the involvement of FIP200 in proliferation and apoptosis. We also examined expression of FIP200 using HCC tissues and the correlation between FIP200 expression and clinical outcome. Methods: The study was conducted using HCC cell lines (HepG2, HuH7, and Hep3B). P53 status in HepG2, HuH7 and Hep3B are wild type, mutant type and deficient types respectively. Expression of endogenous FIP200 was assessed by western blotting. To investigate antitumor function, we carried out BrdU incorporation assay with transfected FIP200. TUNEL was carried out for identification of apoptosis. We also reviewed 14 patients who had undergone initial liver resection for HCC. Immunohistochemistry analysis for FIP200 was performed and we investigated the FIP200 expression levels according to differentiation degree of HCC tissues. Results: Endogenous FIP200 was detected in all cell lines, and those expression levels were different among cell lines. Overexpression of FIP200 significantly decreased BrdU incorporation in HepG2 and HuH7 but not Hep3B. In the study of TUNEL, apoptosis was observed for p53 wild HepG2 transfected with FIP200. In Hep3B, there was no significant difference observed. As for clinical samples, FIP200 were detected in all HCC and non-HCC tissues. FIP200 expression levels in HCC tissues were decreased compared to non-HCC tissues. Furthermore, as differentiation degree poored, those expression levels were decreased in the same tissue as well as in the different tissue. Conclusions: Endogenous FIP200 was expressed in all cell line. Those expression levels were different according to p53 status. Our study demonstrated that FIP200 inhibit proliferation in HCC expressed p53, and induce apoptosis in p53 wild HCC but not p53 deficient HCC. Furthermore, the FIP200 expression levels were significantly associated with differentiation degree. These data suggest that FIP200 plays an important role in promoting tumor progression in HCC. No significant financial relationships to disclose.