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

Tumor necrosis factor alpha (TNFα) 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 reg...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-11, Vol.376 (4), p.748-752
Main Authors: Guardiola-Serrano, Francisca, Haendeler, Judith, Lukosz, Margarete, Sturm, Karsten, Melchner, Harald von, Altschmied, Joachim
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
AGAR
Angiogenesis
APOPTOSIS
CARCINOMAS
Carrier Proteins - genetics
Cell Line, Tumor
Cell Movement - genetics
CELL PROLIFERATION
DNA-Binding Proteins - genetics
Endothelial cells
Gene Expression Regulation, Neoplastic
Gene trapping
GENES
GRHL3
Humans
INFLAMMATION
MACROPHAGES
Migration
Mutagenesis
Neovascularization, Pathologic - genetics
Recombinase
Recombination, Genetic
TNFα
TRANSCRIPTION FACTORS
Transcription Factors - genetics
TRAPPING
Tumor Necrosis Factor-alpha - metabolism
Tumor suppressor
Tumor Suppressor Proteins - genetics
ZC3H10
ZINC
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Summary:Tumor necrosis factor alpha (TNFα) 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 TNFα, we performed a gene trap screen in the mammary carcinoma cell line MCF-7 and recovered 64 unique, TNFα-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 TNFα 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.09.070