%0 Journal Article
%T Down-regulation of PPARgamma1 suppresses cell growth and induces apoptosis in MCF-7 breast cancer cells
%A Yekaterina Y Zaytseva
%A Xin Wang
%A R Chase Southard
%A Natalie K Wallis
%A Michael W Kilgore
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-90
%X We have previously demonstrated that an increase in expression of PPAR¦Ã1 in MCF-7 breast cancer cells is driven by a tumor-specific promoter. Myc-associated zinc finger protein (MAZ) was identified as a transcriptional mediator of PPAR¦Ã1 expression in these cells. In this study, using RNA interference (RNAi) to inhibit PPAR¦Ã1 expression directly or via down-regulation of MAZ, we report for the first time that a decrease in PPAR¦Ã1 expression results in reduced cellular proliferation in MCF-7 breast cancer cells. Furthermore, we demonstrate that these changes in proliferation are associated with a significant decrease in cell transition from G1 to the S phase. Using a dominant-negative mutant of PPAR¦Ã1, ¦¤462, we confirmed that PPAR¦Ã1 acts as a pro-survival factor and showed that this phenomenon is not limited to MCF-7 cells. Finally, we demonstrate that down-regulation of PPAR¦Ã1 expression leads to an induction of apoptosis in MCF-7 cells, confirmed by analyzing Bcl-2 expression and PARP-1 cleavage.Thus, these findings suggest that an increase in PPAR¦Ã1 signaling observed in breast cancer contributes to an imbalance between proliferation and apoptosis, and may be an important hallmark of breast tumorigenesis. The results presented here also warrant further investigation regarding the use of PPAR¦Ã ligands in patients who are predisposed or already diagnosed with breast cancer.Breast cancer is the most common malignancy and the second leading cause of cancer related death among American women [1]. Despite of the fact that recent research efforts have significantly improved the outcome of breast cancer, the complexity and heterogeneity of this disease still urges the necessity to explore new and more specific drug targets. Peroxisome proliferator-activated receptor gamma (PPAR¦Ã), a member of the nuclear-hormone receptor family, has shown potential as a therapeutic target for prevention and treatment of breast cancer. PPAR¦Ã is a ligand-activated transcription factor. Ther
%U http://www.molecular-cancer.com/content/7/1/90