Gene trapping identifies a putative tumor suppressor and a new inducer of cell migration.
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.
Guardiola-Serrano
Francisca
F
Department of Molecular Hematology, University of Frankfurt Medical School, 60590 Frankfurt am Main, Germany.
Haendeler
Judith
J
Lukosz
Margarete
M
Sturm
Karsten
K
Melchner
Harald von
Hv
Altschmied
Joachim
J
D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016296:Mutagenesis; D009389:Neovascularization, Pathologic / Q000235:genetics; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C473143:GRHL3 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; C532885:ZC3H10 protein, human