title: A Western-type diet accelerates tumor progression in an autochthonous mouse model of prostate cancer.
abstract: Epidemiological studies have provided evidence suggesting an important role for diet and obesity in the development of cancer. Specifically, lipid nutrients of the diet have been identified as important regulators of tumor development and progression. In the present study, we have examined the role of dietary fat and cholesterol in the initiation and progression of prostate cancer using the well-characterized TRAMP mouse model. Consumption of a Western-type diet--that is, enriched in both fat and cholesterol--accelerated prostate tumor incidence and tumor burden compared to mice fed a control chow diet. Furthermore, we also show that this diet increased the extent and the histological grade of prostate tumors. These findings were confirmed by the presence of increased levels of protein markers of advanced tumors in prostates obtained from animals fed a Western-type diet compared to those obtained from control animals. Increased lung metastases in animals fed a Western-type diet were also observed. In addition, we found that with a Western diet, animals bearing tumors presented with reduced plasma cholesterol levels compared with animals fed a control diet. Finally, we show that tumors obtained from animals fed a Western-type diet displayed increased expression of the high-density lipoprotein receptor SR-BI and increased angiogenesis. Taken together, our data suggest that dietary fat and cholesterol play an important role in the development of prostate cancer.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA.
authors.forename: Gemma
authors.initials: G
authors.lastname: Llaverias
authors.forename: Christiane
authors.initials: C
authors.lastname: Danilo
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Agnes K
authors.initials: AK
authors.lastname: Witkiewicz
authors.forename: Kristin
authors.initials: K
authors.lastname: Daumer
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Frank
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004032:Diet / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D047368:Tumor Burden; D019366:Western World
chemical_list: D004041:Dietary Fats