Abstract
IntroductionFas/CD95 is a member of the death receptor superfamily that can induce apoptosis and it functions as the key component of the extrinsic death pathway. This study reports on a relevant function of Fas death receptor that can regulate transcription factors p53, MYC, NF-κ B and pro-apoptotic gene PUMA, that are important in intrinsic death pathway in hepatocellular carcinoma (HCC).Material and methodsFor the in vivo study, genes Fas, and FasL from 111 samples (39 HCC, 30 peri-HCC, 31 cirrhosis, and 11 normal) from patients undergoing liver resection without any prior treatments were analysed. For the in vitro study, hepatocytes cell line IHH and human HCC cell lines HepG2, HUH7, JHH6 were used. Apoptosis-induction was performed by using anti-Fas (DX2) at a concentration of 250 ng/ml and 500 ng/ml for 24 hours. Flow cytometry and quantitative real-time PCR were performed to analyse the data.Results and discussionThe expressions of Fas and FasL mRNA were significantly noticed in HCC as compared to normal tissues. FasL mRNA was high expressed in viral-related compared to metabolic-related HCC while Fas was high in HCC tissues without vascular invasion compared to tissues with vascular invasion. For in vitro study, after treatment of anti-CD95, TNF-α was significantly up regulated in HEPG2 compare to IHH cells. Transcription factors p53, MYC and NF-κ B were down regulated in HEPG2 cells while up regulated or no difference change in IHH cells. Pro-apoptotic gene Puma was only up regulated in IHH cell line. Telomerase was up regulated in IHH and significantly down regulated in HEPG2.ConclusionsWe observed a modulation of transcription factors p53, MYC, NF-κ B and pro-apoptotic genes Puma, TNF-α, and Telomerase after induction by CD95 antibody in acute phase treatment for 24 hours. The expression of PUMA and MYC were regulated by the transcription factors p53, thus suggesting the involvement of Fas in p53-dependent apoptosis pathway.
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