title: Role of DLC1 tumor suppressor gene and MYC oncogene in pathogenesis of human hepatocellular carcinoma: potential prospects for combined targeted therapeutics (review).
abstract: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death,             and its incidence is increasing worldwide in an alarming manner. The development             of curative therapy for advanced and metastatic HCC is a high clinical priority.             The HCC genome is complex and heterogeneous; therefore, the identification of             recurrent genomic and related gene alterations is critical for developing clinical             applications for diagnosis, prognosis and targeted therapy of the disease. This             article focuses on recent research progress and our contribution in identifying             and deciphering the role of defined genetic alterations in the pathogenesis of             HCC. A significant number of genes that promote or suppress HCC cell growth have             been identified at the sites of genomic reorganization. Notwithstanding the accumulation             of multiple genetic alterations, highly recurrent changes on a single chromosome             can alter the expression of oncogenes and tumor suppressor genes (TSGs) whose             deregulation may be sufficient to drive the progression of normal hepatocytes             to malignancy. A distinct and highly recurrent pattern of genomic imbalances in             HCC includes the loss of DNA copy number (associated with loss of heterozygosity)             of TSG-containing chromosome 8p and gain of DNA copy number or regional amplification             of protooncogenes on chromosome 8q. Even though 8p is relatively small, it carries             an unusually large number of TSGs, while, on the other side, several oncogenes             are dispersed along 8q. Compelling evidence demonstrates that DLC1, a potent TSG             on 8p, and MYC oncogene on 8q play a critical role in the pathogenesis of human             HCC. Direct evidence for their role in the genesis of HCC has been obtained in             a mosaic mouse model. Knockdown of DLC1 helps MYC in the induction of hepatoblast             transformation in vitro, and in the development of HCC in vivo. Therapeutic interventions,             which would simultaneously target signaling pathways governing both DLC1 and MYC             functions in hepatocarcinogenesis, could result in progress in the treatment of             liver cancer.
authors.affiliation: Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Drazen B
authors.initials: DB
authors.lastname: Zimonjic
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Popescu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D025521:Tumor Suppressor Proteins