title: Lycopene in the prevention of renal cell cancer in the TSC2 mutant Eker rat model.
abstract: Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. Eker rat represents a unique animal model to study RCC since these rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of rapamycin (mTOR) pathway. This study examines the role of a lycopene-rich diet in the development of RCC in the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n=90) were assigned in equal numbers to receive 0, 100 or 200mg/kg of lycopene as part of their daily diet. After 18 months the rats were sacrificed and the kidneys were removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6 and EGFR were performed, as well as hematoxylin-eosin staining for histologic examination of the tumors. Tumors were counted and measured in individual kidneys. Presence of tumor decreased from 94% in control animals to 65% in the experimental group, but the difference was not statistically significant (P<0.12). However, mean numbers of renal carcinomas were statistically significantly decreased in the lycopene-treated rats (P<0.008) when compared to untreated controls. In the lycopene group, tumor numbers decreased (P<0.002) and the numbers tended to decrease linearly (P<0.003) as supplemental lycopene increased from 0 to 200. Control rats fed only basal diet had a greater length of tumors (23.98 mm) than rats fed lycopene supplement groups (12.90 mm and 11.07 mm) (P<0.05). Moreover tumor length decreased (P<0.02) and tumor length tended to decrease linearly (P<0.03) as supplemental lycopene increased from 0 to 200mg/kg. All tumors showed strong staining with antibodies against mTOR, phospho-S6 and EGFR. In conclusion, dietary supplementation with lycopene attenuates the development of renal cell cancers in the predisposed TSC2 mutant Eker rat model. These results suggest that lycopene may play a role in the prevention of RCC.
authors.affiliation: Department of Animal Nutrition, Veterinary Faculty, Firat University, Elazig, Turkey.
authors.forename: Kazim
authors.initials: K
authors.lastname: Sahin
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Cross
authors.affiliation: Department of Animal Nutrition, Veterinary Faculty, Firat University, Elazig, Turkey.
authors.forename: Nurhan
authors.initials: N
authors.lastname: Sahin
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States.
authors.forename: Karina
authors.initials: K
authors.lastname: Ciccone
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States.
authors.forename: Shadeah
authors.initials: S
authors.lastname: Suleiman
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States.
authors.forename: Adeboye O
authors.initials: AO
authors.lastname: Osunkoya
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States.
authors.forename: Viraj
authors.initials: V
authors.lastname: Master
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States.
authors.forename: Wayne
authors.initials: W
authors.lastname: Harris
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States.
authors.forename: Bradley
authors.initials: B
authors.lastname: Carthon
authors.affiliation: Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Mohammad
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States.
authors.forename: Birdal
authors.initials: B
authors.lastname: Bilir
authors.affiliation: DSM, Basel, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Wertz
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States.
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Moreno
authors.affiliation: Molecular Carcinogenesis, Science Park - Research Division, The University of Texas MD Anderson Cancer Center, Smithville, TX, United States.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Walker
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, United States. Electronic address: okucuk@emory.edu.
authors.forename: Omer
authors.initials: O
authors.lastname: Kucuk
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002338:Carotenoids / Q000494:pharmacology*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000077276:Lycopene; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D016588:Anticarcinogenic Agents; D010750:Phosphoproteins; C000624653:TSC2 protein, human; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D002338:Carotenoids; C483803:Egfr protein, rat; D066246:ErbB Receptors; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D000077276:Lycopene
keywords: Eker rat; Lycopene; Renal cell cancer