title: Dietary energy balance modulates prostate cancer progression in Hi-Myc mice.
abstract: Male Hi-Myc mice were placed on three dietary regimens [30% calorie restriction (CR), overweight control (modified AIN76A with 10 kcal% fat), and a diet-induced obesity regimen (DIO) 60 kcal% fat]. All diet groups had approximately similar incidence of hyperplasia and low-grade prostatic intraepithelial neoplasia in the ventral prostate at 3 and 6 months of age. However, 30% CR significantly reduced the incidence of in situ adenocarcinomas at 3 months compared with the DIO group and at 6 months compared with both the overweight control and DIO groups. Furthermore, the DIO regimen significantly increased the incidence of adenocarcinoma with aggressive stromal invasion, as compared with the overweight control group (96% vs. 65%, respectively; P = 0.02) at the 6-month time point. In addition, at both 3 and 6 months, only in situ carcinomas were observed in mice maintained on the 30% CR diet. Relative to overweight control, DIO increased whereas 30% CR reduced activation of Akt, mTORC1, STAT3, and NFκB (p65) in ventral prostate. DIO also significantly increased (and 30% CR decreased) numbers of T-lymphocytes and macrophages in the ventral prostate compared with overweight control. The mRNA levels for interleukin (IL) 1α, IL1β, IL6, IL7, IL23, IL27, NFκB1 (p50), TNFα, and VEGF family members were significantly increased in the ventral prostate of the DIO group compared with both the overweight control and 30% CR diet groups. Collectively, these findings suggest that enhanced growth factor (Akt/mTORC1 and STAT3) and inflammatory (NFκB and cytokines) signaling may play a role in dietary energy balance effects on prostate cancer progression in Hi-Myc mice.
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Blando
authors.forename: Tricia
authors.initials: T
authors.lastname: Moore
authors.forename: Stephen
authors.initials: S
authors.lastname: Hursting
authors.forename: Guiyu
authors.initials: G
authors.lastname: Jiang
authors.forename: Achinto
authors.initials: A
authors.lastname: Saha
authors.forename: Linda
authors.initials: L
authors.lastname: Beltran
authors.forename: Jianjun
authors.initials: J
authors.lastname: Shen
authors.forename: John
authors.initials: J
authors.lastname: Repass
authors.forename: Sara
authors.initials: S
authors.lastname: Strom
authors.forename: John
authors.initials: J
authors.lastname: DiGiovanni
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D031204:Caloric Restriction; D004032:Diet; D004041:Dietary Fats / Q000009:adverse effects; D018450:Disease Progression; D002149:Energy Intake; D004734:Energy Metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D009765:Obesity / Q000150:complications / Q000473:pathology; D050177:Overweight / Q000150:complications / Q000473:pathology; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt