Lab Anim Res.  2013 Mar;29(1):39-47.

Effects of dietary high fat on prostate intraepithelial neoplasia in TRAMP mice

• Park SH
• Chang SN
• Baek MW
• Kim DJ
• Na YR
• Seok SH
• Lee BH
• Kim KS
• Park JH

Abstract

Increased fat intake is known to be a major cause of prostate cancer. In this study, we investigated the effect of dietary high fat on prostate intraepithelial neoplasia using transgenic adenocarcinoma mouse prostate (TRAMP) mice. Six-week-old male TRAMP mice were fed AIN93G (control group, 4.0 kcal/kg, n=6) and AIN93G-HFD (experimental group, 4.8 kcal/kg, n=7) for 10 weeks. Prostate histopathology, urogenital tract (UGT) weight, epididymal white adipose tissue weight, argyrophilic nucleolar organizer regions (AgNORs) counts, and serum leptin levels were examined. AIN93G-HFD fed group showed progressed neoplastic lesions in the prostate (P<0.05) compared to AIN93G fed group. AIN93G-HFD intake resulted in a increase in the weight of UGT (P<0.05) and epididymal white adipose tissue. The number of Ag-NOR positive dots significantly increased in each prostate lobe and final serum leptin levels in AIN93G-HFD fed group were about twice those of AIN93G fed group (P<0.05). Dietary high fat was related to the prostate cancer progression in the early stage of TRAMP mice and increased serum leptin levels, suggesting that the regulation of dietary components could delay the progression of prostate cancer.

Keyword

High fat; prostate cancer; transgenic adenocarcinoma mouse prostate; early progression; Ag-NOR

MeSH Terms

Adenocarcinoma
Adipose Tissue, White
Animals
Humans
Leptin
Male
Mice
Nucleolus Organizer Region
Prostate
Prostatic Neoplasms
Leptin

Figure

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  Figure 1 PCR confirmation of probasin and SV40 transgene in all of the 13 mice used in this study. DNAs were extracted from tails and then analyzed by PCR. PCR was performed using primer pairs that were designed to amplify 600-bp sequences of transgene and 500-bp sequences of mouse casein beta housekeeping gene; and PCR products were separated on 1.5% agarose gel.

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  Figure 2 Criteria for histopathological examination of each prostate lobe in both groups. Distribution of PIN(arrow) was evaluated as focal (A), multifocal (B) and diffuse (C) lesion in hematoxylin and eosin (H&E) stained sections at low magnification (×40) using light microscopy. Scale bar=500 µm.

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  Figure 3 (A) The weight change of AIN93G fed group (n=6) and AIN93G-HFD fed group (n=7) during experimental periods. From 1 week after each types of diet feeding, mean body weight more increased in AIN93G fed group than AIN93G fed group. Each value shows the mean±SD of body weight. *P<0.05. (B) The final mean weight of UG tract. Mean UG tract (Bladder, prostate, seminal vesicle and testis) weight significantly increased in AIN93G-fed group. Each value shows the mean±SD. *P<0.05. (C) In AIN93G-HFD fed group, white epididymal adipose tissue weighted more than that of AIN93G fed group. However, there was no significant difference.

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  Figure 4 Histopathology of each lobe of prostate in both groups. A) Anterior lobe of AIN93G-HFD fed group. Cribriform lesion is projection into lumen (Grade PIN2). B) Dorsal lobe of AIN93G-HFD fed group (grade PIN3). Acinus with lumen filled with proliferation epithelium. C) Lateral lobe of AIN93G-HFD fed group (Grade PIN3). Lumen is also filled with proliferating epithelium. D) Ventral lobe of AIN93G-HFD fed group and lesions with focal papillary projections (Grade PIN1). E) Anterior lobe of AIN93G fed group (Grade PIN2). F) Dorsal lobe of AIN93G fed group (Grade PIN3). G) Lateral lobe of AIN93G fed group (Grade PIN2). H) Ventral lobe of AIN93G fed group showing lesions with focal papillary projections (Grade PIN1). All of the histology assessed in H&E stained sections using light microscopy (×200). Scale bar=100 µm.

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  Figure 5 The mean histopathological scores of each lobe of prostate in both groups. Mean histopathological scores in AIN93G-HFD fed group were significantly higher than AIN93G fed group in lateral and dorsal lobe. Each value shows the mean±SD. *P<0.05.

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  Figure 6 Silver stained prostate tissue of AIN93G-HFD fed group showing increased Ag-NORs count. The arrows indicating black dots mean the Ag-NORs (×400). Scale bar=100 µm.

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  Figure 7 Mean final serum leptin levels of two groups. The serum leptin concentration was measured using mouse leptin EIA kit. Leptin levels were 5.15±1.80 ng/mL in AIN93G fed group and 11.94±5.39 ng/mL in AIN93G-HFD fed group. It was significantly different between two groups. Mean±SD. *P<0.05.

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