Expression of Retinoid Receptor Genes and Proteins in Non-Small-Cell Lung Cancer (original) (raw)
1999, JNCI Journal of the National Cancer Institute
Background: Retinoids can suppress carcinogenesis in high-risk nonneoplastic bronchial lesions and can reduce the risk of second primary nonsmall-cell lung cancer (NSCLC). The effects of retinoids are mediated by nuclear receptors, i.e., the retinoic acid receptors (RAR␣, RAR, and RAR␥) and the retinoid X receptors (RXR␣, RXR, and RXR␥). We investigated whether abnormalities in the in vivo expression of retinoid receptors are observed in NSCLC. Methods: Expression of retinoid receptors in paired specimens of normal and cancerous tissues from the lungs of 76 patients with NSCLC was studied by use of antiretinoid receptor antibodies (except those against RXR␥) and immunohistochemistry. RAR messenger RNAs were analyzed by use of in situ hybridization and by reverse transcriptionpolymerase chain reaction (RT-PCR). Samples were also studied for loss of heterozygosity (LOH) at chromosome 3p24. All P values are two-sided. Results: All studied receptors were expressed in normal lung cells and in high-risk non-neoplastic lesions. In tumor cells, overexpression of RXR␣ and RAR␣ was frequently observed. In contrast, RXR expression decreased in 18% of the tumor specimens. Furthermore, there was a marked decrease in the expression of RAR in 63% of the tumors (P<.0001). Decreased expression of RAR␥ was observed by RT-PCR in 41% of the tumors (P<.0001). LOH at 3p24 was observed in 41% of the tumor specimens from informative patients and in 20% of the non-neoplastic lesions. Conclusions: Expression of RAR␣ and RXR␣ is either normal or elevated in NSCLC. In contrast, a large percentage of tumors show a marked decrease in the expression of RAR, RAR␥, and RXR as well as a high frequency of LOH at 3p24, which was also observed in non-neoplastic lesions. These data suggest that altered retinoid receptor expression may play a role in lung carcinogenesis. [J Natl Cancer Inst 1999;91:1059-66]
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