title: Cyclin D1/cdk4, estrogen receptors α and β, in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis: immunohistochemical study.
abstract: Hyperproliferative cell growth due to cyclin D1/cdk4, marker of cellular proliferation, is considered to be regulated by the expression of estrogen receptors (ERs). We investigated the immunohistochemical expression of cyclin D1/cdk4 and ERs in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced rat gastric carcinogenesis. The gastric cancer incidence and expression of cyclin D1/ckd4 in gastric carcinogenesis were significantly higher in males than females. Although the ERα expression index was similar in both sexes, the ERβ expression in preneoplastic hyperplastic lesions as well as gastric cancers was significantly higher in females than in males. The present study revealed a gender difference in MNNG-induced rat gastric carcinogenesis that seemed to involve the sex difference in cyclin D1/cdk4 expression, and ERβ expression became evident at the preneoplastic promotion stage in gastric carcinogenesis.
authors.affiliation: Department of Toxicology and Biochemistry, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Sagamihara, Cyuo, Kanagawa 252-5201, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Motohashi
authors.forename: Shin
authors.initials: S
authors.lastname: Wakui
authors.forename: Tomoko
authors.initials: T
authors.lastname: Muto
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Masaru
authors.initials: M
authors.lastname: Shirai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hano
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D019938:Cyclin D1 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; C530106:Ccnd1 protein, rat; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008769:Methylnitronitrosoguanidine; D019938:Cyclin D1; C495903:Cdk4 protein, rat; D051358:Cyclin-Dependent Kinase 4