High-calorie diet exacerbates prostate neoplasia in mice with haploinsufficiency of Pten tumor suppressor gene.

Autor:	Liu J; Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA ; Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Ramakrishnan SK; Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA ; Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Khuder SS; Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA ; Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Kaw MK; Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA ; Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Muturi HT; Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA ; Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Lester SG; Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA ; Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Lee SJ; Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA ; Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Fedorova LV; Department of Medicine, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Kim AJ; Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA ; Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Mohamed IE; Department of Medicine, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Gatto-Weis C; Department of Pathology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Eisenmann KM; Department of Biochemistry and Cancer Biology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Conran PB; Department of Pathology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA., Najjar SM; Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA ; Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA.
Jazyk:	angličtina
Zdroj:	Molecular metabolism [Mol Metab] 2015 Jan 02; Vol. 4 (3), pp. 186-98. Date of Electronic Publication: 2015 Jan 02 (Print Publication: 2015).
DOI:	10.1016/j.molmet.2014.12.011
Abstrakt:	Objective: Association between prostate cancer and obesity remains controversial. Allelic deletions of PTEN, a tumor suppressor gene, are common in prostate cancer in men. Monoallelic Pten deletion in mice causes low prostatic intraepithelial neoplasia (mPIN). This study tested the effect of a hypercaloric diet on prostate cancer in Pten (+/-) mice. Methods: 1-month old mice were fed a high-calorie diet deriving 45% calories from fat for 3 and 6 months before prostate was analyzed histologically and biochemically for mPIN progression. Because Pten (+/-) mice are protected against diet-induced insulin resistance, we tested the role of insulin on cell growth in RWPE-1 normal human prostatic epithelial cells with siRNA knockdown of PTEN. Results: In addition to activating PI3 kinase/Akt and Ras/MAPkinase pathways, high-calorie diet causes neoplastic progression, angiogenesis, inflammation and epithelial-mesenchymal transition. It also elevates the expression of fatty acid synthase (FAS), a lipogenic gene commonly elevated in progressive cancer. SiRNA-mediated downregulation of PTEN demonstrates increased cell growth and motility, and soft agar clonicity in addition to elevation in FAS in response to insulin in RWPE-1 normal human prostatic cells. Downregulating FAS in addition to PTEN, blunted the proliferative effect of insulin (and IL-6) in RWPE-1 cells. Conclusion: High-calorie diet promotes prostate cancer progression in the genetically susceptible Pten haploinsufficient mouse while preserving insulin sensitivity. This appears to be partly due to increased inflammatory response to high-caloric intake in addition to increased ability of insulin to promote lipogenesis.
Databáze:	MEDLINE
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