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Open Access Sex-Associated Difference in Estrogen Receptor β Expression in N-Methyl-N′-Nitro-N-Nitrosoguanidine-Induced Gastric Cancers in Rats

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Epidemiologic studies indicate that the incidence of gastric cancer is higher in males than in females. Although the mechanisms mediating this difference are unclear, a role for estrogens has been proposed. We used Western blotting to evaluate the role of estrogen receptor (ER) subtypes ERα and ERβ and proliferating cell nuclear antigen (PCNA) in N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in Wistar rats; ERα and ERβ mRNA levels also were analyzed by quantitative real-time RT-PCR analysis. The incidence of gastric cancer was significantly higher in male than female rats. In both sexes, ERα expression was similar in MNNG-treated cancerous and noncancerous tissues and normal gastric tissue. However, ERβ expression in MNNG-treated cancerous and noncancerous tissues was significantly lower in male rats and higher in female rats than that in normal gastric tissue; MNNG-induced cancerous tissue showed the highest ERβ expression. PCNA expression in MNNG-treated cancerous tissues was higher than that in noncancerous tissues, and was higher in male rats than female rats. Western blotting results were consistent with the mRNA changes determined by quantitative real-time RT-PCR. The present study provides evidence of a sex-associated difference in ERβ and PCNA expression in MNNG-induced gastric cancers in Wistar rats.

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Document Type: Research Article

Affiliations: 1: Department of Toxicology and Biochemistry, Azabu University School of Veterinary Medicine, Kanagawa, Japan; Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan 2: Department of Toxicology and Biochemistry, Azabu University School of Veterinary Medicine, Kanagawa, Japan 3: Drug Safety Testing Center, Saitama, Japan 4: Department of Pathology, The Jikei University School of Medicine, Tokyo, Japan 5: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, Japan 6: School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 7: J-Pharma, Tokyo, Japan

Publication date: 2011-10-01

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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