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Identification of the gene for a novel liver‐related putative tumor suppressor at a high‐frequency loss of heterozygosity region of chromosome 8p23 in human hepatocellular carcinoma
Author(s) -
Liao Cheng,
Zhao Mujun,
Song Hai,
Uchida Kiyoshi,
Yokoyama Kazunari K.,
Li Tsaiping
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.17967
Subject(s) - loss of heterozygosity , biology , hepatocellular carcinoma , gene , cancer research , cell growth , suppressor , tumor suppressor gene , gene expression , chromosome , cell , microbiology and biotechnology , allele , carcinogenesis , genetics
Abstract Human chromosome 8p23 is known as a region that is associated with loss of heterozygosity (LOH), which is frequently deleted in hepatocellular carcinoma (HCC) tissues. We report here the characterization of a gene for a liver‐related putative tumor suppressor (LPTS) localized at 8p23, that was isolated by allelic‐loss mapping and positional candidate cloning. The expression of the gene for LPTS was ubiquitous in normal human tissues, albeit at relatively low levels, whereas levels appeared to be significantly reduced, or sometimes undetectable in HCC cells and neoplastic tissues. Thus, it appeared that LPTS might be involved in the control of cell proliferation. Indeed, we observed the significant suppression of growth and growth arrest of SMMC‐7721 HCC cells after introduction of the gene for LPTS. We also used antisense oligodeoxynucleotides (AS‐ODNs) to suppress the expression of LPTS in normal liver cells L02. Several AS‐ODNs specific for LPTS mRNA significantly enhanced cell growth, whereas control oligodeoxynucleotides (ODNs) did not. Our results suggest that LPTS might be a growth‐inhibitory protein in human hepatocytes.