Expression of retinoid receptor genes and proteins in non-small-cell lung cancer

Abstract

Background: Retinoids can suppress carcinogenesis in high-risk non- neoplastic bronchial lesions and can reduce the risk of second primary non- small-cell lung cancer (NSCLC). The effects of retinoids are mediated by nuclear receptors, i.e., the retinoic acid receptors (RARα, RARβ, and RARγ) and the retinoid X receptors (RXRα, RXRβ, and RXRγ). 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 RXRγ) and immunohistochemistry. RAR messenger RNAs were analyzed by use of in situ hybridization and by reverse transcription- polymerase 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 RXRα and RARα was frequently observed. In contrast, RXRβ expression decreased in 18% of the tumor specimens. Furthermore, there was a marked decrease in the expression of RARβ in 63% of the tumors (P