Loss of retinoic acid receptor-beta expression is an early event during esophageal carcinogenesis.
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 beta (RAR-beta). Cell lines that did not express RAR-beta were also resistant to RA. To explore the expression of RAR-beta mRNA in vivo, we analyzed esophageal tissue specimens from 16 normal mucosae, 30 dysplastic lesions, and 157 esophageal tumors by in situ hybridization. RAR-beta 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-beta was expressed in only 57% (17/30) of dysplastic lesions and in 54% (84/157) of carcinomas. Among esophageal carcinomas RAR-beta 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-beta expression is an early event associated with esophageal carcinogenesis and the status of squamous differentiation.
Qiu
H
H
Departments of Clinical Cancer Prevention, Thoracic/Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Zhang
W
W
El-Naggar
A K
AK
Lippman
S M
SM
Lin
P
P
Lotan
R
R
Xu
X C
XC
D000368:Aged; D002454:Cell Differentiation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta