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First published online 21 July 2009
doi: 10.1242/jcs.049619

Journal of Cell Science 122, 2828-2835 (2009)
Published by The Company of Biologists 2009
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Research Article

Regulation of VDR by {Delta}Np63{alpha} is associated with inhibition of cell invasion

Ramakrishna Kommagani1,*, Mary K. Leonard1,*, Stefanie Lewis1, Rose-Anne Romano2, Satrajit Sinha2 and Madhavi P. Kadakia1,{ddagger}

1 Department of Biochemistry and Molecular Biology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45435, USA
2 Department of Biochemistry, State University of New York at Buffalo, NY 14203, USA

{ddagger} Author for correspondence (madhavi.kadakia{at}wright.edu)

Accepted 1 May 2009

The p63 transcription factor has a pivotal role in epithelial morphogenesis. Multiple transcripts of the TP63 gene are generated because of alternative promoter usage and splicing. {Delta}Np63{alpha} is the predominant isoform of p63 observed during epithelial morphogenesis and in human cancers. Loss of {Delta}Np63{alpha} expression has been shown to promote invasiveness in a subset of human cancer cell lines. Here, we studied whether the regulation of VDR by {Delta}Np63{alpha} controls the invasiveness of an epidermoid cancer cell line. We demonstrate that VDR expression is induced by all p63 isoforms, including {Delta}Np63{alpha}. Endogenous {Delta}Np63{alpha} protein was observed to bind to the VDR promoter, and silencing of endogenous {Delta}Np63{alpha} resulted in diminished VDR expression. Although silencing of p63 inhibits VDR expression leading to an increase in cell migration, overexpression of p63 or VDR results in reduced cell migration as a result of increased VDR expression. Therefore, it is conceivable that p63 inhibits cell invasion by regulating VDR expression. Finally, we observed that expression of p63 and VDR overlaps in the wild-type mouse skin, but a reduced or complete absence of VDR expression was observed in skin from p63-null mice and in p63-null mouse embryonic fibroblasts. In conclusion, we demonstrate a direct transcriptional regulation of VDR by {Delta}Np63{alpha}. Our results highlight a crucial role for VDR in p63-mediated biological functions.

Key words: {Delta}Np63{alpha}, VDR, Cell invasion


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