Life Sciences BG | TPA-induced upregulation of TBX3 is mediated by AP-1 and contributes to breast cancer cell migration.

English

TPA-induced upregulation of TBX3 is mediated by AP-1 and contributes to breast cancer cell migration.

The T-box transcription factor, TBX3, provides an important link between embryonic development and cancer. TBX3 mediates limb, mammary gland and heart development and in humans, mutations resulting in haploinsufficiency of TBX3 lead to the ulnar-mammary syndrome. Importantly, the de-regulation of TBX3 gene expression has been linked to several cancers where it acts to suppress senescence, and promotes proliferation and tumour invasion. Despite the negative impact of de-regulated TBX3 expression as seen by developmental defects and cancer, surprisingly little is known about the regulation of the TBX3 gene. Here we show that the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induces TBX3 protein and mRNA levels in a PKC-dependent manner via the activator protein 1 (AP-1) transcription factors c-Jun and JunB. Furthermore, these AP-1 factors are shown to mediate the activation of the TBX3 gene by binding a non-consensus TPA-response element in the TBX3 promoter in vitro and in vivo. We also demonstrate that TBX3 contributes to the TPA-induced migration previously observed for the MCF-7 breast epithelium cancer cell line. Our data reveal a previously unidentified pathway that upregulates TBX3 expression and provides additional evidence that increased levels of TBX3 contributes to metastasis.

Read the original article at BJ Cell.

Published: Nov 2010, Updated: 7th Nov

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