Cytochrome P450 aromatase gene (CYP19) expression in gastric cancer

Abstract

The secretion of biologically active estrogen through the conversion of circulating precursor androgens has been suggested to play important roles in the pathophysiology of estrogen-dependent carcinomas. In the present study, we examined aromatase expression in gastric carcinoma. Nineteen specimens of gastric carcinoma were obtained from Japanese patients at the Department of Surgery, Tottori University Hospital, Japan. Nontumoral tissues adjacent to the carcinoma were also available for analysis. The histological features of the gastric carcinomas were as follows: 8 intestinal-type and 11 diffuse-type adenocarcinomas. Tissue specimens removed at surgery were used for the preparation of RNA or for immunohistochemical analysis. Six cell lines derived from human gastric cancers were also used as a model system. Using conventional and real-time reverse transcription-polymerase chain reactions, aromatase mRNA expression and promoter usage were assayed. Immunohistochemical analysis was performed using an anti-aromatase antibody. We demonstrated the molecular basis of aromatase mRNA expression, which depended on three proximal promoters in tumoral and nontumoral tissues, for the first time. The tumoral tissues exhibited positive staining for anti-aromatase antibody. At the same time, positive staining was also observed in nontumoral mucosa, predominantly in the parietal cells. We provide evidence suggesting a mechanism for the secretion of estrogen through the conversion of a precursor androgen in tumoral and nontumoral tissues in the stomach.