title: Mechanistic basis for the chemopreventive effects of black raspberries at a late stage of rat esophageal carcinogenesis.
abstract: The present study used a postinitiation protocol to investigate molecular mechanisms by which black raspberries (BRBs) influence the late stages of N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in rats. F344 rats were injected with NMBA and then fed either control diet or a diet containing 5% BRB powder. Control rats were injected with DMSO/water (20:80), the vehicle for NMBA. Esophagi from control, NMBA- and NMBA + BRB-treated rats were collected at 35 wk for histopathological, molecular, and immunohistochemical analyses. Treatment with 5% BRBs reduced the number of dysplastic lesions and the number and size of esophageal papillomas in NMBA-treated rats. When compared to esophagi from control rats, NMBA treatment led to the differential expression of 4807 genes in preneoplastic esophagus (PE) and 17 846 genes in esophageal papillomas. Dietary BRBs modulated 626 of the 4807 differentially expressed genes in PE and 625 of the 17 846 differentially expressed genes in esophageal papillomas towards normal levels of expression. In both PE and in papillomas, BRBs modulated the mRNA expression of genes associated with carbohydrate and lipid metabolism, cell proliferation and death, and inflammation. In these same tissues, BRBs modulated the expression of proteins associated with proliferation, apoptosis, inflammation, angiogenesis, and both cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Interestingly, matrix metalloproteinases involved in tissue invasion and metastasis, and proteins associated with cell-cell adhesion, were also modulated by BRBs. This is the first report of the effects of berries on the expression of genes associated with the late stages of rat esophageal carcinogenesis.
authors.affiliation: Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43240, USA.
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Wang
authors.forename: Alan A
authors.initials: AA
authors.lastname: Dombkowski
authors.forename: Claire
authors.initials: C
authors.lastname: Seguin
authors.forename: Claudia
authors.initials: C
authors.lastname: Rocha
authors.forename: Daniela
authors.initials: D
authors.lastname: Cukovic
authors.forename: Anju
authors.initials: A
authors.lastname: Mukundan
authors.forename: Cassandra
authors.initials: C
authors.lastname: Henry
authors.forename: Gary D
authors.initials: GD
authors.lastname: Stoner
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives; D015232:Dinoprostone / Q000097:blood; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005638:Fruit / Q000737:chemistry*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027824:Rosaceae / Q000737:chemistry*; D013997:Time Factors
chemical_list: D018952:Antigens, CD34; D051017:Apoptosis Regulatory Proteins; D019394:Ki-67 Antigen; D028321:Plant Preparations; D007975:Leukotriene B4; C014707:nitrosobenzylmethylamine; D015232:Dinoprostone; D004128:Dimethylnitrosamine