Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatocellular carcinoma suppressor 1 (HCCS1) gene was identified by both positional cloning from a predominant region of loss of heterozygosity (17p13.3) in liver cancer and by functional screening for genes affecting cell proliferation in large-scale transfection assays. Its overexpression results in inhibition of cell proliferation in cell culture and tumor growth in nude mice. To understand its transcription regulation, the promoter architecture has been dissected in detail. The major start of transcription was mapped by primer extension to a C residue, 177 nucleotides upstream of the ATG codon. By assessing the promoter activity of a set of linker-scanning mutants of the minimal promoter (-60 to +148 region) in a transient transfection assay, we found that the +1 to + 40 region is critical to HCCS1 gene transcription, containing binding sites for transcription factors NF-kappaB (-21 to +7 and +40 to +26), p53 (+29 to +9) and ETS (+4 to +20 and +23 to +39). Biochemical and molecular analyses revealed that the ETS transcription factors ETS-2 and Elf-1 bind to the two ETS sites in situ and contribute significantly to the transcriptionally active state of the HCCS1 gene, while NF-kappaB, p53 and two other members of the ETS family (ETS-1 and NERF2) appear to play little role. Our observations provide insight into the mechanistic aspects of HCCS1 transcription regulation.
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PMID:Transcription of the putative tumor suppressor gene HCCS1 requires binding of ETS-2 to its consensus near the transcription start site. 1695 16

We previously demonstrated that hepatocellular carcinoma suppressor 1 (HCCS1) exerts potent anti-tumor activity. In this study, we constructed a new dual tumor-targeting oncolytic adenovirus vector, PD55-HCCS1, in which E1A was driven by the promoter of progression elevated gene-3, which is hepatoma-specific, and a CMV-HCCS1 expression cassette replaced E1B55. The PD55-HCCS1-mediated selective expression of E1A and HCCS1 in hepatoma cells and tumor-selective cytotoxicity in vitro and in vivo demonstrated the strongest inhibition of BEL-7404 cell xenografts in nude mice among a number of control Ad vectors. These data indicated the efficacy and safety of the PD55-HCCS1 system for HCC treatment.
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PMID:Potent anti-hepatoma efficacy of HCCS1 via dual tumor-targeting gene-virotherapy strategy. 1894 98