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- Title
Differential expression of retinoic acid receptors in normal and malignant esophageal tissues.
- Authors
Kumar, Anupam; Kaur, Jatinder; Chattopadhyay, Tushar Kant; Mathur, Meera; Ralhan, Ranju
- Abstract
The chemopreventive and chemotherapeutic activities of retinoids may be attributed to their ability to modulate growth, differentiation and apoptosis of epithelial cells, suppress or reverse epithelial carcinogenesis. Many of these effects of retinoids result from modulation of genes by two distinct classes of retinoid receptors: RARs and RXRs, alterations in their expression may lead to tumorigenesis. To determine whether alterations in expression of retinoid receptors are related to the development of esophageal squamous cell carcinomas (ESCCs), the expression of RARα, β γ and RXRα was studied in 50 untreated primary esophageal carcinomas and 19 distant normal tissues by immunohistochemistry. RARβ expression was observed in 18/50 (36%) ESCCs, while 16/19 (84%) of matched histologically normal esophageal tissues displayed RARβ immunopositivity (p=0.001, OR=3.405). Significant increase in RARα immunopositivity was observed in ESCCs (40/50; 80%) as compared to normal tissues (9/19 cases; 47%) (p=0.008; OR=2.77). RARγ expression was observed in ESCCs (37/50cases; 74%) as compared to normal tissues (16/19; 84%); without significant difference. However, poorly differentiated esophageal cancer showed marked decrease in RARγ immunopositivity (p=0.017; OR=6.0). Interestingly, increased expression of RXRα was observed in 43/50 (86%) ESCCs in comparison with (10/19; 53%) normal tissues (p=0.003; OR=3.09). Logistic regression analysis revealed RARγ/RXRα+ phenotype as most significantly associated with dedifferentiation of the tumor (p=0.014; OR=11.0). The hallmark of the study was the significant increase in expression of RARα and RXRα proteins and loss of expression of RARβ protein in ESCCs in comparison with the distant normal epithelia.
- Subjects
ESOPHAGEAL cancer; TRETINOIN; RETINOIDS; CARCINOGENESIS; CANCER
- Publication
Journal of Experimental Therapeutics & Oncology, 2004, Vol 4, Issue 1, p1
- ISSN
1359-4117
- Publication type
Article