title: Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma.
abstract: Tensins are a new family of proteins that act as an important link among extracellular matrix, actin cytoskeleton, and signal transduction and have been implicated in human cancers. Tensin2 was initially identified in a search for new tensin family members that share extensive sequence homology with tensin1. Tensin2 was highly expressed in liver tissues. A recent study reported that one of the splicing variants of tensin2, variant 3, promotes cell migration. In the present study, we aimed to elucidate the role of variant 3 in hepatocarcinogenesis by assessing the expression of variant 3 mRNA in hepatocellular carcinoma (HCC) tissue and ectopically expressing variant 3 in HCC cell lines. Analysis of variant 3 expression in human HCC tissue revealed it was overexpressed in 46% (23/50) of tumor tissues as compared with the corresponding nontumorous livers. High expression of variant 3 was significantly associated with venous invasion (P = .037), tumor microsatellite formation (P = .022), and tumor nonencapsulation (P = .049). Our ectopic expression study showed that variant 3 significantly promoted the cell growth and motility of HCC cells. The clonal transfectants of variant 3 were more closely packed and resulted in a higher saturation density than in the control vector transfectants. Variant 3 expression also enhanced the proliferation rate in culture and in vivo tumorigenicity in nude mice. In conclusion, we reveal a novel role for variant 3 in the progression of HCC and suggest the feasibility of elevated variant 3 expression as a tumor progression marker for HCC.
authors.affiliation: Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Judy Wai Ping
authors.initials: JW
authors.lastname: Yam
authors.forename: Frankie Chi Fat
authors.initials: FC
authors.lastname: Ko
authors.forename: Chung-Yiu
authors.initials: CY
authors.lastname: Chan
authors.forename: Tai-On
authors.initials: TO
authors.lastname: Yau
authors.forename: Edmund Kwok Kwan
authors.initials: EK
authors.lastname: Tung
authors.forename: Thomas Ho-Yin
authors.initials: TH
authors.lastname: Leung
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Jin
authors.forename: Irene Oi-Lin
authors.initials: IO
authors.lastname: Ng
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000070876:Tensins; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D012333:RNA, Messenger; D000070876:Tensins; C452816:TNS2 protein, human; D010749:Phosphoprotein Phosphatases; C511707:Tns2 protein, mouse; D010744:Phosphoric Monoester Hydrolases