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Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis.
Cancer Prev Res (Phila). 2014 Dec; 7(12):1228-39.CP

Abstract

Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4 to 10 weeks of age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone repletion (2.5 mg/kg/d initiated 1 week after castration). Ten-week-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia. Of the 200 prostate cancer-related genes measured by quantitative NanoString, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P < 0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared with WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P < 0.0001) compared with intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways is reduced by lycopene feeding (Srd5a1) and by tomato feeding (Srd5a2, Pxn, and Srebf1). In addition, tomato feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, whereas lycopene feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk.

Authors+Show Affiliations

Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Interdisciplinary Nutrition Program, The Ohio State University, Columbus, Ohio.Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Interdisciplinary Nutrition Program, The Ohio State University, Columbus, Ohio.Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Department of Statistics, The Ohio State University, Columbus, Ohio.Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio. steven.clinton@osumc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25315431

Citation

Wan, Lei, et al. "Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-related Gene Expression During Early TRAMP Prostate Carcinogenesis." Cancer Prevention Research (Philadelphia, Pa.), vol. 7, no. 12, 2014, pp. 1228-39.
Wan L, Tan HL, Thomas-Ahner JM, et al. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis. Cancer Prev Res (Phila). 2014;7(12):1228-39.
Wan, L., Tan, H. L., Thomas-Ahner, J. M., Pearl, D. K., Erdman, J. W., Moran, N. E., & Clinton, S. K. (2014). Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis. Cancer Prevention Research (Philadelphia, Pa.), 7(12), 1228-39. https://doi.org/10.1158/1940-6207.CAPR-14-0182
Wan L, et al. Dietary Tomato and Lycopene Impact Androgen Signaling- and Carcinogenesis-related Gene Expression During Early TRAMP Prostate Carcinogenesis. Cancer Prev Res (Phila). 2014;7(12):1228-39. PubMed PMID: 25315431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis. AU - Wan,Lei, AU - Tan,Hsueh-Li, AU - Thomas-Ahner,Jennifer M, AU - Pearl,Dennis K, AU - Erdman,John W,Jr AU - Moran,Nancy E, AU - Clinton,Steven K, Y1 - 2014/10/14/ PY - 2014/10/16/entrez PY - 2014/10/16/pubmed PY - 2015/8/1/medline SP - 1228 EP - 39 JF - Cancer prevention research (Philadelphia, Pa.) JO - Cancer Prev Res (Phila) VL - 7 IS - 12 N2 - Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild-type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4 to 10 weeks of age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone repletion (2.5 mg/kg/d initiated 1 week after castration). Ten-week-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia. Of the 200 prostate cancer-related genes measured by quantitative NanoString, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (P < 0.05). In TRAMP, expression of Birc5, Mki67, Aurkb, Ccnb2, Foxm1, and Ccne2 is greater compared with WT and is decreased by castration. In parallel, castration reduces Ki67-positive staining (P < 0.0001) compared with intact and testosterone-repleted TRAMP mice. Expression of genes involved in androgen metabolism/signaling pathways is reduced by lycopene feeding (Srd5a1) and by tomato feeding (Srd5a2, Pxn, and Srebf1). In addition, tomato feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, whereas lycopene feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. SN - 1940-6215 UR - https://www.unboundmedicine.com/medline/citation/25315431/Dietary_tomato_and_lycopene_impact_androgen_signaling__and_carcinogenesis_related_gene_expression_during_early_TRAMP_prostate_carcinogenesis_ L2 - http://cancerpreventionresearch.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=25315431 DB - PRIME DP - Unbound Medicine ER -