Transcription factor Dlx2 protects from TGFβ-induced cell-cycle arrest and apoptosis.

ABSTRACT: Acquiring resistance against transforming growth factor β (TGFβ)-induced growth inhibition at early stages of carcinogenesis and shifting to TGFβ's tumour-promoting functions at later stages is a pre-requisite for malignant tumour progression and metastasis. We have identified the transcription factor distal-less homeobox 2 (Dlx2) to exert critical functions during this switch. Dlx2 counteracts TGFβ-induced cell-cycle arrest and apoptosis in mammary epithelial cells by at least two molecular mechanisms: Dlx2 acts as a direct transcriptional repressor of TGFβ receptor II (TGFβRII) gene expression and reduces canonical, Smad-dependent TGFβ signalling and expression of the cell-cycle inhibitor p21(CIP1) and increases expression of the mitogenic transcription factor c-Myc. On the other hand, D

SUBMITTER: Yilmaz M 

PROVIDER: S-EPMC3230376 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature