Loss of Retinoic Acid Receptor-{beta} Expression Is an Early Event during Esophageal Carcinogenesis

摘要

We recently observed that growth inhibition of esophageal cancer cells by retinoic acid (RA) was associated with both constitutive expression and RA-induced up-regulation of RA receptor ß (RAR-ß). Cell lines that did not express RAR-ß were also resistant to RA. To explore the expression of RAR-ß mRNA in vivo, we analyzed esophageal tissue specimens from 16 normal mucosae, 30 dysplastic lesions, and 157 esophageal tumors by in situ hybridization. RAR-ß was detected in 88% (14/16) of normal esophageal tissues and in 96% (96/100) of distant normal esophageal mucosa from cancer specimens. In contrast, RAR-ß was expressed in only 57% (17/30) of dysplastic lesions and in 54% (84/157) of carcinomas. Among esophageal carcinomas RAR-ß mRNA was expressed in 62% (26/42) of well-differentiated, 54% (27/50) of moderately differentiated, and only 29% (4/14) of poorly differentiated SCCs. Our data suggest that the loss of RAR-ß expression is an early event associated with esophageal carcinogenesis and the status of squamous differentiation.