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 haplo-insufficiency of TBX3 lead to 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. In the present paper, we show that the phorbol ester PMA increases TBX3 protein and mRNA levels in a protein kinase C-dependent manner via the AP-1 (activator protein 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 PMA-response element in the TBX3 promoter in vitro and in vivo. We also demonstrate that TBX3 contributes to the PMA-induced migration previously observed for the MCF-7 breast epithelium cancer cell line. Our present results reveal a previously unidentified pathway that up-regulates TBX3 expression and provides additional evidence that increased levels of TBX3 contribute to metastasis.
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January 2011
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Research Article|
December 15 2010
PMA-induced up-regulation of TBX3 is mediated by AP-1 and contributes to breast cancer cell migration
Shaheen Mowla;
Shaheen Mowla
*Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa
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Romaney Pinnock;
Romaney Pinnock
*Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa
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Virna D. Leaner;
Virna D. Leaner
†Department of Medical Biochemistry, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa
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Colin R. Goding;
Colin R. Goding
‡Ludwig Institute for Cancer Research, Oxford University, Old Road Campus, Headington, Oxford OX3 7DQ, U.K.
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Sharon Prince
Sharon Prince
1
*Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa
1To whom correspondence should be addressed (email Sharon.prince@uct.ac.za).
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Publisher: Portland Press Ltd
Received:
June 21 2010
Revision Received:
September 27 2010
Accepted:
October 13 2010
Accepted Manuscript online:
October 13 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 433 (1): 145–153.
Article history
Received:
June 21 2010
Revision Received:
September 27 2010
Accepted:
October 13 2010
Accepted Manuscript online:
October 13 2010
Citation
Shaheen Mowla, Romaney Pinnock, Virna D. Leaner, Colin R. Goding, Sharon Prince; PMA-induced up-regulation of TBX3 is mediated by AP-1 and contributes to breast cancer cell migration. Biochem J 1 January 2011; 433 (1): 145–153. doi: https://doi.org/10.1042/BJ20100886
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