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

Molecular Metabolism
Jehnan LiuSonia M Najjar

Abstract

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. 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. 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. Downregulati...Continue Reading

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Citations

Sep 17, 2015·Endocrine-related Cancer·Emma H Allott, Stephen D Hursting
Dec 13, 2017·Cold Spring Harbor Perspectives in Medicine·Giorgia Zadra, Massimo Loda
Jun 26, 2020·Frontiers in Nutrition·Ajit Venniyoor
May 6, 2019·Journal of Clinical Medicine·Shintaro NaritaTomonori Habuchi

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Methods Mentioned

BETA
Fluorescence
transfection
PCR

Software Mentioned

Image J
SAS
GraphPad Prism

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