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Overexpression of RbAp46 facilitates stress-induced apoptosis and suppresses tumorigenicity of neoplastigenic breast epithelial cells.
- Source :
-
International journal of cancer [Int J Cancer] 2003 Jul 20; Vol. 105 (6), pp. 762-8. - Publication Year :
- 2003
-
Abstract
- We have found previously that the retinoblastoma (Rb) suppressor associated protein 46 (RbAp46) is a gene upregulated by the Wilms' tumor suppressor, WT1, and functions as a potent growth inhibitor. To investigate the effect of RbAp46 overexpression on early development of breast cancer, we established stable cell lines from neoplastigenic breast epithelial cells, MCF10AT3B, a cell line derived from a model of human proliferative disease, to constitutively express exogenous RbAp46. We have found that expression of RbAp46 suppressed colony formation of MCF10AT3B cells in soft-agar, and inhibited tumor formation of these cells in nude mice. Expression of RbAp46 sensitized MCF10AT3B cells to apoptosis induced by serum deprivation and hydrocortisone withdrawal. Furthermore, we have found that the c-Jun NH2-terminal kinase (JNK) pathway and GADD45, a growth arrest- and DNA damage-inducible gene, are constitutively activated in RbAp46-expressing cells. Our data suggested that high levels of RbAp46 expression inhibit the tumorigenicity of neoplastigenic breast epithelial cells by facilitating JNK-dependent apoptotic cell death. Our data also suggested that dysregulation of RbAp46 gene may be involved in the early development of breast cancer.<br /> (Copyright 2003 Wiley-Liss, Inc.)
- Subjects :
- Animals
Breast cytology
Carrier Proteins genetics
Carrier Proteins metabolism
Cell Division
Cell Line, Transformed
Epithelial Cells cytology
Epithelial Cells metabolism
Female
Humans
Intracellular Signaling Peptides and Proteins
JNK Mitogen-Activated Protein Kinases
Mammary Neoplasms, Experimental metabolism
Mammary Neoplasms, Experimental pathology
Mice
Mice, Nude
Mitogen-Activated Protein Kinases metabolism
Nuclear Proteins genetics
Nuclear Proteins metabolism
Protein Biosynthesis
Retinoblastoma-Binding Protein 7
Transfection
Tumor Suppressor Proteins genetics
Tumor Suppressor Proteins metabolism
GADD45 Proteins
Apoptosis
Carrier Proteins physiology
Mammary Neoplasms, Experimental etiology
Nuclear Proteins physiology
Proteins
Tumor Suppressor Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0020-7136
- Volume :
- 105
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 12767060
- Full Text :
- https://doi.org/10.1002/ijc.11148