The new research on tumor suppressor gene in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related death in the world.The carcinogenesis of HCC is multifactorial,multifunctional and multistage.Tumor suppressor gene therapy is one of the strategies,it is mainly used to make use of tumor suppressor gene groups which can inhibit the cell growth,to prevent the expression of oncogenes or to resume the function of anti-oncogenes.But so far,there is not a particular gene to be a main tumor suppressor gene in HCC.Therefore,it is necessary to study on the new anti-oncogenes to explain pathogenesis of liver cancer and seek for the newly effective target to carry on liver cancer gene therapy.PTEN(phosphatase and tensin homolog deleted on chromosome ten)was discovered as a tumor suppressor gene.It functions as a protein tyrosine phosphatase and as a lipid phosphatase.As a lipid phosphatase,PTEN antagonizes PI3K/Akt signaling by dephosphorylating the D3 position of the inositol ring of phosphatidylinositol 3,4,5-trisphosphate(PIP3),to generate phosphatidylinositol-4,5,-biphosphate(PIP2).On the other hand,as a protein tyrosine phosphatase,PTEN can dephosphorylate itself,focal adhesion kinase(FAK)and the platelet derived growth factor receptor,involves in the migration,adhension of cells.Many researches have been testified that there is a higher frequency of negative expression of PTEN protein in hepatocellular carcinoma,the negative correlation between expression of PTEN gene and differential grade,clinic stage of HCC indicated that in activation of PTEN gene maybe a late incidence in the development of hepatocellular carcinoma and may play an important role in the genesis and development of some hepatocellular carcinoma.KLF6,a member of Krupple-like gene family,a ubiquitously expressed zinc finger transcription factor,has an important role in regulating cell growth and differentiation.Several experiments have been proved that the genetic events of tumor suppressor gene mutation and loss of allele of KLF6 gene were presented frequently in HCC.These results indicate that KLF6 may be a candidate tumor suppressor gene of HCC and plays a role during the hepatocarcinogenesis and progression of HCC.P16 gene is also called multiple tumor suppressor l(MTS1).It is the specific inhibitor of CDK4(cyclin dependent kinase 4,CDK 4).It can induce cell cycle arrest in G1 to S phase by inhibiting CDK4.The p16 gene acts in the HCC development and deletion,mutation or methylation of p16 gene are usually found in HCC.In a word,the wild-type p16 may play an important role in tumor suppression and initiate cell senescence beginning by the mechanism of inducing cell telomeric shortening and growth arrest.