Gene trapping identifies a putative tumor suppressor and a new inducer of cell migration

Biochem Biophys Res Commun. 2008 Nov 28;376(4):748-52. doi: 10.1016/j.bbrc.2008.09.070. Epub 2008 Sep 22.

Abstract

Tumor necrosis factor alpha (TNFalpha) is a pleiotropic cytokine involved in apoptotic cell death, cellular proliferation, differentiation, inflammation, and tumorigenesis. In tumors it is secreted by tumor associated macrophages and can have both pro- and anti-tumorigenic effects. To identify genes regulated by TNFalpha, we performed a gene trap screen in the mammary carcinoma cell line MCF-7 and recovered 64 unique, TNFalpha-induced gene trap integration sites. Among these were the genes coding for the zinc finger protein ZC3H10 and for the transcription factor grainyhead-like 3 (GRHL3). In line with the dual effects of TNFalpha on tumorigenesis, we found that ZC3H10 inhibits anchorage independent growth in soft agar suggesting a tumor suppressor function, whereas GRHL3 strongly stimulated the migration of endothelial cells which is consistent with an angiogenic, pro-tumorigenic function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mutagenesis
  • Neovascularization, Pathologic / genetics
  • Recombination, Genetic
  • Transcription Factors / genetics*
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Suppressor Proteins / genetics*

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • GRHL3 protein, human
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Proteins
  • ZC3H10 protein, human