Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma

Authors

  • Judy Wai Ping Yam,

    1. Department of Pathology, SH Ho Foundation Research Laboratories and Hong Kong Jockey Club Clinical Research Centre, The University of Hong Kong, Pokfulam, Hong Kong
    Search for more papers by this author
  • Frankie Chi Fat Ko,

    1. Department of Pathology, SH Ho Foundation Research Laboratories and Hong Kong Jockey Club Clinical Research Centre, The University of Hong Kong, Pokfulam, Hong Kong
    Search for more papers by this author
  • Chung-Yiu Chan,

    1. Department of Pathology, SH Ho Foundation Research Laboratories and Hong Kong Jockey Club Clinical Research Centre, The University of Hong Kong, Pokfulam, Hong Kong
    Search for more papers by this author
  • Tai-On Yau,

    1. Department of Pathology, SH Ho Foundation Research Laboratories and Hong Kong Jockey Club Clinical Research Centre, The University of Hong Kong, Pokfulam, Hong Kong
    Search for more papers by this author
  • Edmund Kwok Kwan Tung,

    1. Department of Pathology, SH Ho Foundation Research Laboratories and Hong Kong Jockey Club Clinical Research Centre, The University of Hong Kong, Pokfulam, Hong Kong
    Search for more papers by this author
  • Thomas Ho-Yin Leung,

    1. Department of Pathology, SH Ho Foundation Research Laboratories and Hong Kong Jockey Club Clinical Research Centre, The University of Hong Kong, Pokfulam, Hong Kong
    Search for more papers by this author
  • Dong-Yan Jin,

    1. Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
    Search for more papers by this author
  • Irene Oi-Lin Ng

    Corresponding author
    1. Department of Pathology, SH Ho Foundation Research Laboratories and Hong Kong Jockey Club Clinical Research Centre, The University of Hong Kong, Pokfulam, Hong Kong
    • Room 127B, University Pathology Building, Department of Pathology, University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China
    Search for more papers by this author
    • fax: (852) 2872-5197


  • Potential conflict of interest: Nothing to report.

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. (HEPATOLOGY 2006;44:881–90.)

Ancillary