Evaluation Of Oncogenes BcI-2 And Tgf-6. In Chronic Hepatitis C Patients In Relationship To Hepatocellular Carcinoma
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Relatively little is known about the biochemical mechanisms controlling proliferation and neoplastic transformation of HCC even though it is one of the most prevalent and malignant cancers in humans. Bc1-2 oncoprotein can prolong cell survival by blocking apoptosis without affecting cellular proliferation. Transforming growth factor & (TGF- 6) is alleged to play a role in malignant progression as well as normal cell growth in an autocrine manner. Patients and Methods:The present study was carried out to investigate the kinetics of 13c1-2, TGF-. at and alpha-fetoprotein (AFP) release in sera, ascitic fluid and liver tissue from patients with chronic hepatitis C virus (HCV) and those with hepatocellualr carcinoma (HCC). The impact of these biomarkers on the development of HCC was also investigated. Results: The obtained results revealed that serum Bc1-2 was significantly increased (P<0.001) each of the chronic HCV and HCC patients as compared to the normal control group. There was no significant difference between ascitic fluid Bc1-2 and serum BcI-2 in HCV groups. BcI-2 was also estimated in 8 liver cell lysates of patients with HCV it was 5442.8+1307.4 U /106 cells. This may suggest that the antiapoptotic oncoprotein Bc1-2 may provide hepatocytes with sufficient time in the inflamed tissue to accumulate the specific gene mutations that culminate cancer. Thiswork showed that serum TGF- 6 was significantly increased in HCV and HCC patients (P<0.001) groups as compared to the normal control one. Moreover, there. was significant increase (P<0.001) in TGF- & . level in HCV patients as compared to those with HCC. This finding could suggest that TGF- 6. might be the primary markerto start the process of carcinogenesis, however, low levels of TGF- 6.6. may be neededto the progress of malignancy. Moreover, necrosis in the malignant tissue may lead to decreased production of TGF- 6. bythe liver tissue. Serum TGF- a was significantly increased (P<0.05) in HCV patients with liver cirrhosis as compared to HCV withoutcirrhosis. This might suggest that the hepatocyte regeneration occurring in cirrhosismight contribute to the increased serum TGF- 6 levels in HCV patients with liver cirrhosis. In conclusion, Bc1-2 oncoprotein expression in hepatocytes in HCV suggests that the available mechanism of apoptosis may be suppressed by Bc1-2. The increased expression of BcI-2 oncoprotein in HCC, by its antiapoptotic action isessential for carcinogenesis to proceed to malignancy. Although the increased expression of BcI-2 oncoprotein in HCC suggests that Bc1-2 may be involved inhepatocarcinogenesis, further investigation through molecular techniques isnecessary, in order to define the exact role of apoptosis-related genes in this neoplastic process.