Expression of nuclear retinoid receptors in normal, premalignant and malignant gastric tissues determined by in situ hybridization

Retinoids exhibit multiple functions through interaction with nuclear retin oid receptors and have growth-suppressive activity on gastric cancer cells. To better understand the roles of nuclear retinoid receptors during gastri c carcinogenesis, we have used in situ hybridization to investigate express ion of retinoic acid receptors (RARs) and retinoid x receptors (RXRs) in pr emalignant and malignant formalin-fixed paraffin-embedded gastric tissues. Histological sections of eight normal, 17 distal normal and nine gastric ca ncer tissues were hybridized with non-radioactive RNA probes for subtypes o f RAR and RXR. Expression of RAR alpha, RAR beta, RAR gamma, RXR alpha and RXR beta was found in most cell types in gastric mucosa tissues from normal individuals as well as in distal normal tissues from cancer patients. Expr ession of RAR alpha and RAR beta were found in three and seven cancer tissu es, respectively, and levels of RXR alpha mRNA were significantly decreased in poorly differentiated cancer tissues. Among the five investigated nucle ar retinoid receptors, only expression of RAR alpha mRNA was significantly decreased in intestinal metaplasia, dysplasia and cancer tissues when compa red to adjacent normal tissues. In conclusion. normal gastric mucosa expres sed both RARs and RXRs, which supports the physiological role of retinoic a cid on normal gastric mucosa. The decrease in RAR alpha expression in prema lignant and malignant gastric tissues suggests a significant role of RAR al pha during gastric carcinogenesis.