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Lab Invest. 2010 Feb;90(2):222-33. doi: 10.1038/labinvest.2009.128. Epub 2009 Nov 30.

Runx2 regulates survivin expression in prostate cancer cells.

Author information

1
Programs in Genetic, Molecular and Cellular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.

Abstract

Previously we described that bone morphogenetic protein-7 (BMP7) could protect prostate cancer C4-2B cells from serum starvation-induced apoptosis via survivin induction. Here, for the first time, we identify Runx2 as a key regulator of survivin transcription. In C4-2B cells grown normally, suppression of Runx2 reduced survivin expression. Using ChIP assays, two regions of the survivin promoter, -1953 to -1812 (I) and -1485 to -1119 (II) encompassing consensus Runx-binding sites were examined. Runx2 was found to be associated with both regions, with a stronger affinity to region-I. In serum-starved cells neither region was occupied, but BMP7 restored association to region-II and not region-I. In reporter assays, transcription activity by BMP7 was significantly reduced when sequences including binding sites of region-II were deleted. Additionally, Runx2 expression was enhanced by BMP7 in these cells. Along with a strong survivin expression, a trend in increased Runx2 expression in human prostate cancer cells and tissues was noted. In the conditional Pten-knockout mouse, Runx2 level increased with growth of prostate tumor. The data define a novel role of Runx2 in regulating survivin expression in malignant epithelial cells and identify it as a critical factor in BMP signaling that protects cancer cells against apoptosis.

PMID:
19949374
PMCID:
PMC2815261
DOI:
10.1038/labinvest.2009.128
[Indexed for MEDLINE]
Free PMC Article

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