Candidate genes involved in enhanced growth of human prostate cancer under high fat feeding identified by microarray analysis

Abstract

BACKGROUND. Several studies have suggested that a high fat diet (HFD) may be a risk factor of prostate cancer (PCa). As a first step to delineate the molecular mechanisms underlying the enhanced progression of PCa under HFD, we investigated the differential gene expressions of a human PCa xenograft under HFD and a low fat diet (LFD). METHODS. LNCaP cells were subcutaneously injected in 20 nude mice, which were equally divided into two groups, the HFD group and LFD group. Oligonucleotide microarray analyses were performed using mice xenografts from HFD and LFD, and the results of candidate genes with a significant differential expression were validated by quantitative RT-PCR experiments. As for insulin-like growth factor I receptor (IGF-IR), protein expression levels were further examined by immunohistochemistry in xenograft tissues and in 78 radical prostatectomy specimens. RESULTS. Tumor volume and serum PSA levels were significantly higher in the HFD group than in the LFD group (P < 0.001 and P = 0.006, respectively). We found 64 up-regulated genes (0.19%) and 14 down-regulated genes (0.04%) with more than twofold differences in the HFD xenograft. IGF-IR, TNFRSF, and LPL showed striking differences in the quantitative RT-PCR experiment. Immunostaining further revealed marked enhanced IGF-IR expression in the HFD xenograft. In human PCa, the lowest IGF-IR immunoreactivity group tended to have the lowest body mass index in both normal and PCa epithelium. CONCLUSION. HFD induced remarkable up- and down-regulation of mRNA of a substantial number of genes. Furthermore, the IGF-I system may be involved in the HFD-associated enhanced progression of PCa. © 2008 Wiley-Liss, Inc.