Back to Search
Start Over
Peroxisome proliferator-activated receptor alpha in the human breast cancer cell lines MCF-7 and MDA-MB-231.
- Source :
-
Molecular carcinogenesis [Mol Carcinog] 2002 Aug; Vol. 34 (4), pp. 165-71. - Publication Year :
- 2002
-
Abstract
- Peroxisome proliferator-activated receptor (PPAR) alpha is a ligand-activated transcription factor that has been linked with rodent hepatocarcinogenesis. It has been suggested that PPARalpha mRNA expression levels are an important determinant of rodent hepatic tumorigenicity. Previous work in rat mammary gland epithelial cells showed significantly increased PPARalpha mRNA expression in carcinomas, suggesting the possible role of this isoform in rodent mammary gland carcinogenesis. In this study we sought to determine whether PPARalpha is expressed and dynamically regulated in human breast cancer MCF-7 and MDA-MB-231 cells. Having established the presence of PPARalpha in both cell types, we then examined the consequence of PPARalpha activation, by its ligands Wy-14,643 and clofibrate, on proliferation. With real-time reverse transcriptase-polymerase chain reaction, we showed that PPARalpha mRNA was dynamically regulated in MDA-MB-231 cells and that PPARalpha activation significantly increased proliferation of the cell line. In contrast, PPARalpha expression in MCF-7 cells did not change with proliferation during culture and was present at significantly lower levels than in MDA-MB-231 cells. However, PPARalpha ligand activation still significantly increased the proliferation of MCF-7 cells. The promotion of proliferation in breast cancer cell lines following PPARalpha activation was in stark contrast to the effects of PPARgamma-activating ligands that decrease proliferation in human breast cancer cells. Our results established the presence of PPARalpha in human breast cancer cell lines and showed for the first time that activation of PPARalpha in human breast cancer cells promoted proliferation. Hence, this pathway may be significant in mammary gland tumorigenesis.<br /> (Copyright 2002 Wiley-Liss, Inc.)
- Subjects :
- Breast Neoplasms genetics
Breast Neoplasms pathology
Cell Division drug effects
Clofibrate pharmacology
Female
Gene Expression Regulation, Neoplastic
Humans
Peroxisome Proliferators pharmacology
Pyrimidines pharmacology
RNA, Messenger analysis
Receptors, Cytoplasmic and Nuclear drug effects
Receptors, Cytoplasmic and Nuclear genetics
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors drug effects
Transcription Factors genetics
Tumor Cells, Cultured
Breast Neoplasms metabolism
Receptors, Cytoplasmic and Nuclear metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0899-1987
- Volume :
- 34
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 12203367
- Full Text :
- https://doi.org/10.1002/mc.10061