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

Tumor necrosis factor alpha (TNF alpha) 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 TNF alpha, we performed a gene trap screen in the mammary carcinoma cell line MCF-7 and recovered 64 unique, TNF alpha-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 TNF alpha 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. (C) 2008 Elsevier Inc. All rights reserved.