title: Human tetraspanin transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein is overexpressed in hepatocellular carcinoma and accelerates tumor cell growth.
abstract: The human transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein (TM4SF4/il-TMP) was originally cloned as an intestinal and liver tetraspan membrane protein and mediates density-dependent cell proliferation. The rat homolog of TM4SF4 was found to be up-regulated in regenerating liver after two-thirds hepatectomy and overexpression of TM4SF4 could enhance liver injury induced by CCl(4). However, the expression and significance of TM4SF4/il-TMP in liver cancer remain unknown. Here, we report that TM4SF4/il-TMP is frequently and significantly overexpressed in hepatocellular carcinoma (HCC). Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that TM4SF4/il-TMP mRNA and protein levels were up-regulated in ∼80% of HCC tissues. Immunohistochemical analysis of a 75 paired HCC tissue microarray revealed that TM4SF4/il-TMP was significantly overexpressed in HCC tissues (P< 0.001), and high immunointensity of TM4SF4/il-TMP tended to be in well-to-moderately differentiated HCC compared with poorly differentiated tumors. Functional studies showed that overexpression of TM4SF4/il-TMP in QGY-7701 and BEL-7404 HCC cell lines through stable transfection of TM4SF4 expression plasmid significantly promoted both cell growth and colony formation of HCC cells. Reduction of TM4SF4/il-TMP expression in QGY-7701 and BEL-7404 cells by stably transfecting TM4SF4 antisense plasmid caused great inhibition of cell proliferation. Our findings suggest that TM4SF4/il-TMP has the potential to be biomarker in HCC and plays a crucial role in promotion of cancer cell proliferation.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Leiming
authors.initials: L
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Qiu
authors.forename: Liang
authors.initials: L
authors.lastname: Da
authors.forename: Pierre
authors.initials: P
authors.lastname: Tiollais
authors.forename: Zaiping
authors.initials: Z
authors.lastname: Li
authors.forename: Mujun
authors.initials: M
authors.lastname: Zhao
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D059470:Tetraspanins / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C109139:TSPAN4 protein, human; D059470:Tetraspanins