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, 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.
Davis
J Nathan
JN
Department of Biochemistry and Molecular Biology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Rogers
Donna
D
Adams
Lisa
L
Yong
Thomas
T
Jung
Jette S
JS
Cheng
Bing
B
Fennell
Katie
K
Borazanci
Erkut
E
Moustafa
Yara W
YW
Sun
Amanda
A
Shi
Runhua
R
Glass
Jonathan
J
Mathis
J Michael
JM
Williams
B Jill
BJ
Meyers
Shari
S
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D041681:NIH 3T3 Cells; D009368:Neoplasm Transplantation; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
C493692:CBFB protein, human; D050658:Core Binding Factor beta Subunit