| First Author | Skelhorne-Gross G | Year | 2012 |
| Journal | Carcinogenesis | Volume | 33 |
| Issue | 7 | Pages | 1412-20 |
| PubMed ID | 22581835 | Mgi Jnum | J:190771 |
| Mgi Id | MGI:5449673 | Doi | 10.1093/carcin/bgs173 |
| Citation | Skelhorne-Gross G, et al. (2012) Stromal adipocyte PPARgamma protects against breast tumorigenesis. Carcinogenesis 33(7):1412-20 |
| abstractText | Peroxisome proliferator-activated receptor (PPAR)gamma regulates the expression of genes essential for fat storage, primarily through its activity in adipocytes. It also has a role in carcinogenesis. PPARgamma normally stops the in vivo progression of 7,12-dimethylbenz[a]anthracene (DMBA)-mediated breast tumours as revealed with PPARgamma haploinsufficient mice. Since many cell types associated with the mammary gland express PPARgamma, each with unique signal patterns, this study aimed to define which tissues are required for PPARgamma-dependent antitumour effects. Accordingly, adipocyte-specific PPARgamma knockout (PPARgamma-A KO) mice and their wild-type (PPARgamma-WT) controls were generated, and treated with DMBA for 6 weeks to initiate breast tumorigenesis. On week 7, mice were randomized to continue on normal chow diet or one supplemented with rosiglitazone (ROSI), and followed for 25 weeks for tumour outcomes. In PPARgamma-A KO versus PPARgamma-WT mice, malignant mammary tumour incidence was significantly higher and mammary tumour latency was decreased. DMBA + ROSI treatment reduced average mammary tumour volumes by 50%. Gene expression analyses of mammary glands by quantitative real-time polymerase chain reaction and immunofluorescence indicated that untreated PPARgamma-A KOs had significantly decreased BRCA1 expression in mammary stromal adipocytes. Compared with PPARgamma-WT mice, serum leptin levels in PPARgamma-A KOs were also significantly higher throughout the study. Together, these data are the first to suggest that in vivo PPARgamma expression in mammary stromal adipocytes attenuates breast tumorigenesis through BRCA1 upregulation and decreased leptin secretion. This study supports a protective effect of activating PPARgamma as a novel chemopreventive therapy for breast cancer. |
