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Loss of retinoic acid receptor-beta expression is an early event during esophageal carcinogenesis
H Qiu1, W Zhang, A K El-Naggar
1Departments of Clinical Cancer Prevention, Thoracic/Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Abstract:
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.
Insights
Loss of retinoic acid receptor beta (RAR-beta) expression is linked to esophageal cancer development. This early event impacts carcinogenesis and squamous differentiation in esophageal tissues.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Retinoic acid (RA) inhibits esophageal cancer cell growth.
- This inhibition correlates with retinoic acid receptor beta (RAR-beta) expression.
- RAR-beta expression is crucial for RA sensitivity in esophageal cancer cells.
Purpose of the Study:
- To investigate the in vivo expression of RAR-beta mRNA in normal, dysplastic, and cancerous esophageal tissues.
- To determine the association between RAR-beta expression and esophageal carcinogenesis.
- To explore the relationship between RAR-beta expression and the degree of squamous differentiation.
Main Methods:
- In situ hybridization was used to analyze RAR-beta mRNA expression.
- Esophageal tissue specimens included normal mucosa, dysplastic lesions, and esophageal tumors (squamous cell carcinomas).
- Expression levels were correlated with clinicopathological features, including differentiation status.
Main Results:
- RAR-beta mRNA was detected in 88% of normal esophageal tissues and 96% of adjacent normal mucosa.
- Expression was significantly lower in dysplastic lesions (57%) and carcinomas (54%).
- RAR-beta expression decreased with poor squamous cell carcinoma differentiation (29% in poorly differentiated vs. 62% in well-differentiated).
Conclusions:
- Loss of RAR-beta expression is an early event in esophageal carcinogenesis.
- Reduced RAR-beta expression is associated with decreased squamous differentiation in esophageal tumors.
- RAR-beta may serve as a biomarker for esophageal cancer progression.