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Overexpression of activin A in stage IV colorectal cancer
  1. S Wildia,
  2. J Kleeffa,
  3. H Maruyamaa,
  4. C A Maurerb,
  5. M W Büchlerb,
  6. M Korca
  1. aDivision of Endocrinology, Diabetes, and Metabolism, Departments of Medicine, Biological Chemistry, and Pharmacology, University of California, Irvine, California, USA, bDepartment of Visceral and Transplantation Surgery, University of Bern, 3010 Bern, Switzerland
  1. Dr M Korc, Division of Endocrinology, Diabetes, and Metabolism, Medical Sciences I, C240, University of California, Irvine, CA 92697, USA.mkorc{at}uci.edu

Abstract

BACKGROUND AND AIMS Activins and inhibins are dimeric polypeptides that belong to the transforming growth factor beta (TGF-β) superfamily and that bind to transmembrane receptors with serine/threonine kinase activity. The aim of this study was to characterise, in colon cancer cell lines and in normal and malignant human colon tissues, levels of expression of inhibin subunits that are involved in activin/inhibin dimer formation, and of the type I and II activin receptors (actRI and actRII).

METHODS Expression of inhibin subunits and activin receptors was analysed by northern blot analysis. Inhibin βA and activin receptor expression were also assessed by use of polymerase chain reaction (PCR). In addition, activin A/inhibin βA localisation in human colon samples was assessed by immunohistochemistry and in situ hybridisation.

RESULTS Inhibin βA mRNA was expressed in CaCo2 cells but not in SW 837 or SW 1463 cells whereas inhibin βB and inhibin α were below the level of detection. In contrast, all four activin receptors were present in the three cell lines. Colon cancers overexpressed inhibin βA mRNA in comparison with normal colon, and this overexpression was greatest in stage IV tumours. ActRIb mRNA levels were slightly higher in the normal colon than in cancer tissues. By immunohistochemistry and in situ hybridisation, activin A and inhibin βA mRNA were present in the mucosal epithelial cells in normal tissues from patients with stage I disease but were either absent or weakly present in normal tissues from patients with stage IV disease. Conversely, they were present at weak to moderate levels in stage I cancers but at high levels in stage IV cancers.

CONCLUSIONS Our findings indicate that activin A is overexpressed in human colorectal tumours, especially in stage IV disease, raising the possibility that activin A may have a role in advanced colorectal cancer.

  • colorectal cancer
  • activin βA
  • northern blot analysis
  • Abbreviations used in this paper

    TGF-β
    transforming growth factor beta
    actRI
    activin receptor type I
    actRII
    activin receptor type II
    FBS
    fetal bovine serum
    DMEM
    Dulbecco's modified Eagle's medium
    PCR
    polymerase chain reaction
    BSA
    bovine serum albumin
    MTT
    3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
    RT
    reverse transcription
    PBS
    phosphate buffered saline
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  • Abbreviations used in this paper

    TGF-β
    transforming growth factor beta
    actRI
    activin receptor type I
    actRII
    activin receptor type II
    FBS
    fetal bovine serum
    DMEM
    Dulbecco's modified Eagle's medium
    PCR
    polymerase chain reaction
    BSA
    bovine serum albumin
    MTT
    3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
    RT
    reverse transcription
    PBS
    phosphate buffered saline
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