Effect of excess body adiposity on the expression of genes involved in early steps of mammary carcinogenesis on diet-induced obese female rats

Abstract

Introduction: Obesity is increasing worldwide and is associated with higher risk for some cancers. However, the mechanisms underlying this association are unclear. Because the obesity microenvironment could promote the onset of carcinogenesis, the aim of this study was to evaluate the association between excess body adiposity and the expression of genes related to the activation of early steps of tumor promotion on the mammary gland. Methods: Three weeks-old female Sprague-Dawley rats were fed a high fat diet (DIO: 60% Kcal/g fat, n = 14) or standard chow (LEAN: 3% Kcal/g fat, n = 15) for 10 weeks. Body weight and food intake were measured weekly. After sacrifice, retroperitoneal fat tissue was weighed and mammary tissue was extracted for qRT-PCR analysis. Genes associated with cell proliferation (Survivin/BIRC5 and MYC), DNA repair (TP53), and antioxidant protection (GSTM2, ALDH3A1) were quantified. Results: The DIO group showed a body weight 14.1% higher than LEAN group (p < 0.001). These differences were reflected on higher retroperitoneal fat content on DIO (3.22 ± 0.89g) vs. LEAN group (2.33 ± 0.52g; p = 0.012). Interestingly, DIO rats showed a higher gene expression for Survivin (∆68.2%), MYC (∆50.1%), TP53 (∆40.5%), ALDH3A1 (∆74.1%), and GSTM2 (∆25.7%) with respect to LEAN group. Conclusion: These data show that obesity is associated with changes potentially involved in early steps of tumor promotion, as shown by an increase in cellular proliferation and DNA damage related genes, even before detecting histological changes on the mammary tissue of obese female individuals. Further studies are needed to elucidate weather reducing body weight might be a therapeutic strategy to prevent this process.