Tgif1 is a transcriptional corepressor that limits TGF responsive gene expression. TGF signaling has antiproliferative effects in several cell types, generally resulting in a G1 arrest. Mouse embryo fibroblasts (MEFs) are primary cells with limited life-span, that senesce after several passages in culture.
Premature senescence and increased TGFβ signaling in the absence of Tgif1.
Specimen part
View SamplesThe Runx genes are important in development and cancer, where they can act either as oncogenes or tumour supressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias toward genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins reflecting the marked effects of Runx on cell adhesion.
Gene array analysis reveals a common Runx transcriptional programme controlling cell adhesion and survival.
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