Constitutive expression of Rb associated protein 46 (RbAp46) reverts transformed phenotypes of breast cancer cells.
The retinoblastoma (Rb) suppressor associated protein 46 (RbAp46) is a subunit of chromatin modifying and remodeling complexes. Previously, we found that RbAp46 functions as a potent growth inhibitor. It is also a downstream effector of the Wilms' tumor suppressor, WT1. The findings that expression levels of WT1 were down-regulated in breast cancer cell lines and in subsets of primary breast tumors led us to investigate the possible role of RbAp46 in breast cancer tumorigenesis. Here, we found that RbAp46 expression levels were decreased in five established breast cancer cell lines compared to a normal mammary gland epithelial cell line. To investigate the effect of constitutive expression of RbAp46 on the transformed phenotypes of breast cancer cells, we established stable cell lines that constitutively express exogenous RbAp46 using three breast cancer cell lines, MCF-7, MDA-MB-231 and MDA-MB-436. We have found that RbAp46 expression suppressed colony formation of these breast cancer cells in soft-agar, and inhibited tumor formation of these cells in nude mice. Our data demonstrated that constitutive RbAp46 expression suppresses the transformed phenotypes of breast cancer cells, and suggested that dysregulation of RbAp46 expression may contribute to breast cancer tumorigenesis.
Zhang
Teng-Fei
TF
Creighton University Medical Center, 2500 California Plaza, Omaha, NE 68178, USA.
Yu
Shui-Qing
SQ
Deuel
Thomas F
TF
Wang
Zhao-Yi
ZY
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D056524:Retinoblastoma-Binding Protein 7; D014162:Transfection
D002352:Carrier Proteins; D009687:Nuclear Proteins; C490746:RBBP7 protein, human; C096378:Rbbp7 protein, mouse; D056524:Retinoblastoma-Binding Protein 7