Association of Core-Binding Factor β With the Malignant Phenotype of Prostate and Ovarian Cancer Cells

Core binding factor (CBF) is a transcription factor complex that plays roles in development, stem-cell homeostasis, and human disease. CBF is a heterodimer composed of one of three DNA-binding RUNX proteins plus the non-DNA-binding protein, CBF beta. Recent studies have showed that the RUNX factors exhibit complex expression patterns in prostate, breast, and ovarian cancers, and CBF has been implicated in the control of cancer-related genes. However, the biologic roles of CBF in solid tumors have not been fully elucidated. To test whether CBF is required for the malignant phenotype of various epithelial cancers, we used lentiviral delivery of CBF beta-specific shRNA to significantly decrease CBF beta expression in two prostate cancer cell lines (PPC1 and PC-3) and the SKOV-3 ovarian cancer cell line. We found that knockdown of CBF beta significantly inhibited anchorage independent growth of each cell line. Further, CBF beta knockdown in PPC1 cells suppressed xenograft tumor growth compared to controls. Mice injected with SKOV-3 ovarian cancer cells knocked-down for CBF beta exhibited a survival time similar to control mice. However, human cells recovered from the ascites fluid of these mice showed CBF beta expression levels similar to those from mice injected with control SKOV-3 cells, suggesting that CBF beta knockdown is incompatible with tumor cell growth. Gene expression profiling of CBF beta knockdown cells revealed significant changes in expression in genes involved in various developmental and cell signaling pathways. These data collectively suggest that CBF beta is required for malignancy in some human cancers. J. Cell. Physiol. 225: 875-887, 2010. (C) 2010 Wiley-Liss, Inc.