Epidemiological studies suggest that a high fat diet for more than one generation is associated with an increased risk of prostate cancer. A more complete understanding of the molecular basis for prostate cancer initiation, promotion and progression by dietary fat is essential for the design of rational programs for prostate cancer prevention and treatment. We have maintained ACI rats on a high beef fat diet (22.52% by weight) for two generations (mothers and male pups) and observed that 2nd-generation male rats develop prostatic neoplasia at a higher incidence, and earlier in life, than rats on a control, 5% fat diet. It is significant that rats on the high beef fat diet developed neoplasia in the dorsal lobes of the prostate, as the dorsal lobe of the rat prostate is homologous to the peripheral zone of the human prostate, where prostate cancer is most prevalent. All animal studies and histological analyses have been completed and we have prepared RNA from dorsal prostates of 6, 12 and 18-month-old 2nd-generation rats. We now propose to analyze the molecular differences in the dorsal prostates of rats maintained on a high fat diet, compared to rats on a control diet to follow gene expression through the progressive molecular stages of diet-induced prostatic neoplasia. We propose to use Affymetrix microarrays (approximately 7000 genes) to identify differences in mRNA expression profiles in the dorsal prostates of rats on high beef fat and control diets. Further we propose to use northern blots and immunohistochemistry to confirm data obtained using microarrays and to identify the cell types differentially expressing the genes in question. The successful completion of these experiments will contribute to our understanding of the molecular basis of diet-associated prostate cancer. Further, it can potentially identify intermediate biomarkers that are modulated by diet and are relevant to human prostate cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA088982-01
Application #
6226333
Study Section
Nutrition Study Section (NTN)
Program Officer
Poland, Alan P
Project Start
2001-02-05
Project End
2003-01-31
Budget Start
2001-02-05
Budget End
2002-01-31
Support Year
1
Fiscal Year
2001
Total Cost
$156,500
Indirect Cost
Name
New York Medical College
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595
Reyes, Ismail; Tiwari, Raj; Geliebter, Jan et al. (2007) DNA microarray analysis reveals metastasis-associated genes in rat prostate cancer cell lines. Biomedica 27:190-203
Reyes, Ismael; Reyes, Niradiz; Iatropoulos, Michael et al. (2005) Aging-associated changes in gene expression in the ACI rat prostate: Implications for carcinogenesis. Prostate 63:169-86
Reyes, Niradiz; Reyes, Ismael; Tiwari, Raj et al. (2004) Effect of linoleic acid on proliferation and gene expression in the breast cancer cell line T47D. Cancer Lett 209:25-35
Reyes, Niradiz; Iatropoulos, Michael; Mittelman, Abraham et al. (2002) Microarray analysis of diet-induced alterations in gene expression in the ACI rat prostate. Eur J Cancer Prev 11 Suppl 2:S37-42