gamma-Catenin expression is reduced or absent in a subset of human lung cancers and re-expression inhibits transformed cell growth

Oncogene. 2002 Oct 24;21(49):7497-506. doi: 10.1038/sj.onc.1205963.


Lung cancer is a heterogeneous disease categorized into multiple subtypes of cancers which likely arise from distinct patterns of genetic alterations and disruptions. Precedent exists for a role of beta-catenin, a downstream component of the Wnt signaling pathway that serves as a transcriptional co-activator with TCF/LEF, in several human cancers including colon carcinomas. In this study, we observed that beta-catenin was highly and uniformly expressed in a panel of NSCLC cell lines and primary lung tumors. By contrast, gamma-catenin was weakly expressed or absent in several NSCLC cell lines and immunohistochemical analysis of primary NSCLC tumors revealed negligible to weak gamma-catenin staining in approximately 30% of the specimens. Treatment of NSCLC cells expressing reduced gamma-catenin protein with 5-aza-2'-deoxycytidine (5aza2dc), a DNA methylation inhibitor, or trichostatin A (TSA), a histone deacetylase inhibitor, increased gamma-catenin protein content in NSCLC cells with low gamma-catenin expression. Significantly, the activity of a beta-catenin/TCF-dependent luciferase reporter was markedly elevated in the NSCLC cell lines that underexpressed gamma-catenin relative to those lines that highly expressed gamma-catenin. Moreover, transfection of these cells with a gamma-catenin expression plasmid reduced the elevated TCF activity by 85% and strongly inhibited cell growth on tissue culture plastic as well as anchorage-independent growth in soft agar. This study shows that gamma-catenin can function as an inhibitor of beta-catenin/TCF-dependent gene transcription and highlights gamma-catenin as a potentially novel tumor suppressor protein in a subset of human NSCLC cancers.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell Division / genetics*
  • Cell Transformation, Neoplastic / genetics*
  • Cytoskeletal Proteins / metabolism*
  • Desmoplakins
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Trans-Activators / metabolism
  • Tumor Cells, Cultured
  • beta Catenin
  • gamma Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Desmoplakins
  • JUP protein, human
  • Trans-Activators
  • beta Catenin
  • gamma Catenin