Journal article
AP2 Transcription Factors Regulate Expression of CRABPII in Hormone Responsive Breast Carcinoma
The Journal of surgical research, Vol.138(1), pp.71-78
2007
DOI: 10.1016/j.jss.2006.07.002
PMID: 17187826
Abstract
The AP2 transcription factor family is a set of developmentally regulated, retinoic acid (RA) inducible genes, which regulate expression of estrogen receptor-alpha (ERα) in breast carcinoma. We hypothesized that AP2 factors regulate a set of genes characteristic of the hormone responsive breast cancer phenotype. To better understand the role of AP2 factors in hormone responsive breast cancer, we sought to identify AP2-target genes in breast epithelial cells.
Overexpression of AP2 factors was achieved in human mammary epithelial cells (HMECs) using adenoviral vectors. AP2 target genes were identified by comparative hybridization to cDNA microarrays containing 30,000 human genes. Expression patterns were confirmed by Northern and Western blot and by elimination of AP2 using siRNA. Potential regulatory elements in promoters of target genes were identified by DNase I hypersensitive site mapping.
Comparative cDNA microarray hybridization identified a set of genes induced by overexpression of AP2α and AP2γ in HMECs. The up-regulation of cellular retinoic acid-binding protein 2 (CRABPII), EST-1, and ECM1 was induced by overexpression of AP2α, AP2γ, or a chimeric AP2 factor in which the activation domain of AP2α was replaced by the activation domain of herpesvirus VP16. Interestingly, hormone unresponsive MDA-MB-231 cells were resistant to CRABPII induction by any of the AP2 factors. Elimination of AP2γ in MCF7 cells resulted in a significant reduction in CRABPII expression. AP2α induced DNase I hypersensitive sites in the promoter of the CRABPII gene at −5000 bp, which corresponds to the site of action of RAR/RXR factors.
AP2 factors regulate CRABPII expression in HMECs and breast cancer cells and accounts for the associated expression of ERα and CRABPII in hormone responsive breast cancer. Because CRABPII mediates growth suppressive effects of RA in breast cancer, the data suggest that AP2 factors have the ability to mediate RA responsiveness through the regulation of CRABP II expression.
Details
- Title: Subtitle
- AP2 Transcription Factors Regulate Expression of CRABPII in Hormone Responsive Breast Carcinoma
- Creators
- Lisa A McPherson - Department of Surgery, Stanford University, Stanford, CaliforniaGeorge W Woodfield - Department of Surgery, University of Iowa, Iowa City, IowaRonald J Weigel - Department of Surgery, Stanford University, Stanford, California
- Resource Type
- Journal article
- Publication Details
- The Journal of surgical research, Vol.138(1), pp.71-78
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.jss.2006.07.002
- PMID
- 17187826
- ISSN
- 0022-4804
- eISSN
- 1095-8673
- Language
- English
- Date published
- 2007
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
- Record Identifier
- 9984024413002771
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