Association of core-binding factor β with the malignant phenotype of prostate and ovarian cancer cells

J. Nathan Davis, Donna Rogers, Lisa Adams, Thomas Yong, Jette S. Jung, Bing Cheng, Katie Fennell, Erkut Borazanci, Yara W. Moustafa, Amanda Sun, Runhua Shi, Jonathan Glass, James Michael Mathis, B. Jill Williams, Shari Meyers

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Abstract

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, CBFβ. 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 CBFβ-specific shRNA to significantly decrease CBFβ expression in two prostate cancer cell lines (PPC1 and PC-3) and the SKOV-3 ovarian cancer cell line. We found that knockdown of CBFβ significantly inhibited anchorage independent growth of each cell line. Further, CBFβ knockdown in PPC1 cells suppressed xenograft tumor growth compared to controls. Mice injected with SKOV-3 ovarian cancer cells knocked-down for CBFβ exhibited a survival time similar to control mice. However, human cells recovered from the ascites fluid of these mice showed CBFβ expression levels similar to those from mice injected with control SKOV-3 cells, suggesting that CBFβ knockdown is incompatible with tumor cell growth. Gene expression profiling of CBFβ knockdown cells revealed significant changes in expression in genes involved in various developmental and cell signaling pathways. These data collectively suggest that CBFβ is required for malignancy in some human cancers.

Original languageEnglish
Pages (from-to)875-887
Number of pages13
JournalJournal of Cellular Physiology
Volume225
Issue number3
DOIs
StatePublished - 1 Dec 2010

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Core Binding Factors
Ovarian Neoplasms
Prostatic Neoplasms
Cells
Phenotype
Tumors
Neoplasms
Cell Line
Growth
Genes
Cell signaling

Cite this

Davis, J. N., Rogers, D., Adams, L., Yong, T., Jung, J. S., Cheng, B., ... Meyers, S. (2010). Association of core-binding factor β with the malignant phenotype of prostate and ovarian cancer cells. Journal of Cellular Physiology, 225(3), 875-887. https://doi.org/10.1002/jcp.22298
Davis, J. Nathan ; Rogers, Donna ; Adams, Lisa ; Yong, Thomas ; Jung, Jette S. ; Cheng, Bing ; Fennell, Katie ; Borazanci, Erkut ; Moustafa, Yara W. ; Sun, Amanda ; Shi, Runhua ; Glass, Jonathan ; Mathis, James Michael ; Williams, B. Jill ; Meyers, Shari. / Association of core-binding factor β with the malignant phenotype of prostate and ovarian cancer cells. In: Journal of Cellular Physiology. 2010 ; Vol. 225, No. 3. pp. 875-887.
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abstract = "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, CBFβ. 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 CBFβ-specific shRNA to significantly decrease CBFβ expression in two prostate cancer cell lines (PPC1 and PC-3) and the SKOV-3 ovarian cancer cell line. We found that knockdown of CBFβ significantly inhibited anchorage independent growth of each cell line. Further, CBFβ knockdown in PPC1 cells suppressed xenograft tumor growth compared to controls. Mice injected with SKOV-3 ovarian cancer cells knocked-down for CBFβ exhibited a survival time similar to control mice. However, human cells recovered from the ascites fluid of these mice showed CBFβ expression levels similar to those from mice injected with control SKOV-3 cells, suggesting that CBFβ knockdown is incompatible with tumor cell growth. Gene expression profiling of CBFβ knockdown cells revealed significant changes in expression in genes involved in various developmental and cell signaling pathways. These data collectively suggest that CBFβ is required for malignancy in some human cancers.",
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Davis, JN, Rogers, D, Adams, L, Yong, T, Jung, JS, Cheng, B, Fennell, K, Borazanci, E, Moustafa, YW, Sun, A, Shi, R, Glass, J, Mathis, JM, Williams, BJ & Meyers, S 2010, 'Association of core-binding factor β with the malignant phenotype of prostate and ovarian cancer cells', Journal of Cellular Physiology, vol. 225, no. 3, pp. 875-887. https://doi.org/10.1002/jcp.22298

Association of core-binding factor β with the malignant phenotype of prostate and ovarian cancer cells. / Davis, J. Nathan; Rogers, Donna; Adams, Lisa; Yong, Thomas; Jung, Jette S.; Cheng, Bing; Fennell, Katie; Borazanci, Erkut; Moustafa, Yara W.; Sun, Amanda; Shi, Runhua; Glass, Jonathan; Mathis, James Michael; Williams, B. Jill; Meyers, Shari.

In: Journal of Cellular Physiology, Vol. 225, No. 3, 01.12.2010, p. 875-887.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Association of core-binding factor β with the malignant phenotype of prostate and ovarian cancer cells

AU - Davis, J. Nathan

AU - Rogers, Donna

AU - Adams, Lisa

AU - Yong, Thomas

AU - Jung, Jette S.

AU - Cheng, Bing

AU - Fennell, Katie

AU - Borazanci, Erkut

AU - Moustafa, Yara W.

AU - Sun, Amanda

AU - Shi, Runhua

AU - Glass, Jonathan

AU - Mathis, James Michael

AU - Williams, B. Jill

AU - Meyers, Shari

PY - 2010/12/1

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