A NOVEL CLONED CANDIDATE TUMOR SUPPRESSOR GENE PLCI AND ITS EXPRESSION IN HUMAN HEPATOCELLULAR CARCINOMA
Objective: To study the role of a newly cloned candidate tumor suppressor gene PLCI in hepatocarcinogenesis and its expression/mutation in human hepatocellular carcinoma (HCC) from Qidong liver cancer risk area, China. Methods: PLCI expression and its role in hepatocarcinogenesis were analyzed on 140 pairs of specimens of HCC/adjacent para-cancerous tissues (PCT) and QGY7701 cells by RT-PCR, immunohistochemistry, Western blot, Northern blot, co-immunoprecipitation and tumorigenicity assays in vivo and in vitro. Its mutation was also investigated using direct sequence analysis. Results: Our results showed that PLCI expression is down-regulated in HCC in comparison with PCT in 93%(132/140) of patients, that there are some differences in sequence in PLCI gene between cancer and para-cancerous tissues, and that the labeling index (LI) in immunochemical assay using anti-PLCI-antibodies is 80.2 ± 8.7 and 6.4 ± 2.8 for PCT and HCC tissues respectively (P < 0.01). PLCI overexpression inhibits DNA synthesis and promote apoptosis in QGY7701 cells, inhibited the growth of transfected cells in soft agar compared with vector transfected control cells (P < 0.01), and results in suppression of tumor formation in vivo. Intracellular binding of PLCI and p53 was shown by coimmunoprecipitation approach. Conclusion: PLCI is a putative tumor suppressor gene and its mutation may result in liver cancer occurrence whilst its expression may suppress the incidence, advancement and invasiveness of HCC in patients from Qidong area, China.
No Comments » Add comments