Runx2 regulates survivin expression in prostate cancer cells

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 the association to region II, not 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 the 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.