title: Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis.
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.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Interdisciplinary Nutrition Program, The Ohio State University, Columbus, Ohio.
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Interdisciplinary Nutrition Program, The Ohio State University, Columbus, Ohio.
authors.forename: Hsueh-Li
authors.initials: HL
authors.lastname: Tan
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Thomas-Ahner
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio. Department of Statistics, The Ohio State University, Columbus, Ohio.
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Pearl
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois.
authors.forename: John W
authors.initials: JW
authors.lastname: Erdman
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Moran
authors.affiliation: 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.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Clinton
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis; D002338:Carotenoids / Q000494:pharmacology*; D004032:Diet; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D002338:Carotenoids; D000077276:Lycopene