Growth and Progression of TRAMP Prostate Tumors in Relationship to Diet and Obesity

Bonorden, Melissa J.L.; Großmann, Matthias; Ewing, Sarah; Rogozina, Olga P.; Ray, Arunima; Nkhata, Katai J.; Liao, D. Joshua; Grande, Joseph P.; Cleary, Margot P.

doi:10.1155/2012/543970

Cited by 20 publications

(25 citation statements)

References 48 publications

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“…We concluded that HFD could promote the development and progression of PCa in TRAMP mice with elevated proinflammatory cytokines levels. Similar findings were also reported in other researches [12][13][14][15].…”

Section: Introductionsupporting

confidence: 92%

Maternal High-Fat Diet Promotes the Development and Progression of Prostate Cancer in Transgenic Adenocarcinoma Mouse Prostate Offspring

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: We aim to investigate the impact of maternal high fat diet (HFD) on the development and progression of prostate cancer (PCa) in transgenic adenocarcinoma mouse prostate (TRAMP) offspring. Methods: The TRAMP model was used, and divided into maternal HFD group and normal diet (ND) group in the present study. Each group contained 36 TRAMP mice. Serum levels of leptin, adiponectin, interleukin (IL) -1α, IL-1β, IL-6, tumor necrosis factor-α and monocyte chemotactic protein-1 were measured by the 20th, 24th and 28th week old through ProcartaPlex Multiplex Immunoassay. Body fat ratio was measured by MiniQMR. Tumor formation rate was measured through hematoxylin and eosin (H&E) staining, and mortality rate was measured meantime. Western blot was applied to determine the levels of Protein Kinase B (Akt) and Phosphatase and tensin homolog (PTEN). Results: The mortality rate of maternal HFD group was significantly higher than that of ND group (P = 0.046). The tumor formation rate was significantly higher in maternal HFD group than in ND group only in 20th week subgroup (P = 0.040). A significant increase of leptin was seen in maternal HFD 20th and 24th week subgroups (P = 0.001 and < 0.001, respectively) and a decrease of adiponectin was seen in maternal HFD 20th and 28th week subgroups (P =0.006 and < 0.001, respectively). Besides, an activated phos-Akt (P-Akt) and deactivated PTEN were observed in maternal HFD group. Conclusions: Maternal HFD could increase the standard serum leptin level, inhibit the expression of PTEN protein, promote P-Akt protein expression, activate the PI3K/Akt pathway, and ultimately promote the development and progression of PCa in TRAMP offspring.

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Section: Introductionsupporting

confidence: 92%

Maternal High-Fat Diet Promotes the Development and Progression of Prostate Cancer in Transgenic Adenocarcinoma Mouse Prostate Offspring

Yang

et al. 2018

Cell Physiol Biochem

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“…These studies utilizing either injectable immortalized human cancer cells [7, 8] or transgenic mice including TRAMP [9, 10, 12], Pten [15] and Hi-Myc [13] have generally shown that prolonged high-fat feeding accelerates prostate cancer progression as demonstrated by increased tumor volume, proliferation, neoplastic progression, epithelial-mesenchymal transition, metastasis and mortality (see review [25]). While supporting a causative link between obesity and prostate cancer progression, it is notable that these oncogene-driven transgenic mouse models do not faithfully model human prostate cancer development.…”

Section: Discussionmentioning

confidence: 99%

“…PC3 or LNCaP) are generally increased in mice rendered obese by high-fat feeding compared with lean mice fed a low-fat diet [7–10], while diet-induced obesity accelerates prostate cancer progression /aggressiveness in transgenic mouse strains of prostate cancer (e.g. TRAMP, Hi-Myc, Pten − /+ ) [9–15]. While these data are convincing, they are limited to immortalized metastatic cell lines and genetically modified mice, and studies using additional models that more closely replicate the biology of human prostate cancer are required to confirm these initial observations.…”

Section: Introductionmentioning

confidence: 99%

Obesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts

Clark

Ascui

et al. 2016

Oncotarget

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There are established epidemiological links between obesity and the severity of prostate cancer. We directly tested this relationship by assessing tumorigenicity of patient-derived xenografts (PDXs) of moderate-grade localized prostate cancer in lean and obese severe combined immunodeficiency (SCID) mice. Mice were rendered obese and insulin resistant by high-fat feeding for 6 weeks prior to transplantation, and PDXs were assessed 10 weeks thereafter. Histological analysis of PDX grafts showed no differences in tumor pathology, prostate-specific antigen, androgen receptor and homeobox protein Nkx-3.1 expression, or proliferation index in lean versus obese mice. Whilst systemic obesity per se did not promote prostate tumorigenicity, we next asked whether the peri-prostatic adipose tissue (PPAT), which covers the prostate anteriorly, plays a role in prostate tumorigenesis. In vitro studies in a cellularized co-culture model of stromal and epithelial cells demonstrated that factors secreted from human PPAT are pro-tumorigenic. Accordingly, we recapitulated the prostate-PPAT spatial relationship by co-grafting human PPAT with prostate cancer in PDX grafts. PDX tissues were harvested 10 weeks after grafting, and histological analysis revealed no evidence of enhanced tumorigenesis with PPAT compared to prostate cancer grafts alone. Altogether, these data demonstrate that prostate cancer tumorigenicity is not accelerated in the setting of diet-induced obesity or in the presence of human PPAT, prompting the need for further work to define the at-risk populations of obesity-driven tumorigenesis and the biological factors linking obesity, adipose tissue and prostate cancer pathogenesis.

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“…However, in vivo studies show that prostate volume and tissue alterations are directly proportional to blood glucose levels and also to body weight [ 22 , 34 ] . Furthermore, Bonorden et al [ 35 ] demonstrated that high-fat diet increased the tumour volume in TRAMP mice. Thus, this investigation shows that after an initial decay a high concentration of palmitate, but not glucose, stimulates proliferation of normal prostate epithelial cells.…”

mentioning

confidence: 99%

AKT and AMPK Activation after High-Fat and High-Glucose In Vitro Treatment of Prostate Epithelial Cells

et al. 2014

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Considering the increasing consumption of saturated fat and glucose in diets worldwide and its possible association to carcinogenesis, this investigation analysed the proliferation profile of nonmalignant human prostate epithelial cells after exposure to elevated levels of fat and glucose. PNT1A cells were cultured with palmitate (100 or 200 μM) and/or glucose (450 mg/dl) for 24 or 48 h. Treated cells were evaluated for viability test and cell proliferation (MTS assay). AKT and AMPK phosphorylation status were analysed by Western blotting. After 24 h of high-fat alone or associated with high-glucose treatment, there was an increase in AMPK and AKT activation associated to unchanged MTS-cell proliferation. Following 48 h of high-fat but not high-glucose alone, cells decreased AMPK activation and maintained elevated AKT levels. These data were associated to increased cell proliferation after further high-fat treatment. After longer high-fat exposure, MTS revealed that cells remained proliferating. High-glucose alone or associated to high-fat treatment was not able to increase cell proliferation and AKT activation. A high-fat medium containing 100 μM of palmitate stimulates proliferation in PNT1A cells by decreasing the activation of AMPK and increasing activation of AKT after longer exposure time. These findings improve the knowledge about the negative effect of high levels of this saturated fatty acid on proliferative disorders of prostate.

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Growth and Progression of TRAMP Prostate Tumors in Relationship to Diet and Obesity

Cited by 20 publications

References 48 publications

Maternal High-Fat Diet Promotes the Development and Progression of Prostate Cancer in Transgenic Adenocarcinoma Mouse Prostate Offspring

Maternal High-Fat Diet Promotes the Development and Progression of Prostate Cancer in Transgenic Adenocarcinoma Mouse Prostate Offspring

Obesity does not promote tumorigenesis of localized patient-derived prostate cancer xenografts

AKT and AMPK Activation after High-Fat and High-Glucose In Vitro Treatment of Prostate Epithelial Cells

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