Runx2 regulates survivin expression in prostate cancer cells
| Autor: | Pradip Roy-Burman, Adam M. Bell, Michael B. Cohen, Shangxin Yang, Minyoung Lim, Chen Zhong |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Programmed cell death Bone Morphogenetic Protein 7 Survivin Protein Array Analysis Core Binding Factor Alpha 1 Subunit Biology Adenocarcinoma Transfection Article Pathology and Forensic Medicine Inhibitor of Apoptosis Proteins 03 medical and health sciences Prostate cancer Mice 0302 clinical medicine Runx2 Internal medicine Cell Line Tumor medicine Animals Humans Molecular Biology 030304 developmental biology 0303 health sciences apoptosis Cancer Prostatic Neoplasms Cell Biology medicine.disease prostate cancer Up-Regulation Endocrinology Apoptosis Cell culture 030220 oncology & carcinogenesis Cancer cell embryonic structures Cancer research Microtubule-Associated Proteins |
| Zdroj: | Laboratory investigation; a journal of technical methods and pathology |
| ISSN: | 1530-0307 0023-6837 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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