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Expression of retinoid receptor genes and proteins in non-small-cell lung cancer
E Picard1, C Seguin, N Monhoven
1Laboratoire d'Anatomie Pathologique, Centre Hospitalier Universitaire de Nancy, France.
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 (RARalpha, RARbeta, and RARgamma) and the retinoid X receptors (RXRalpha, RXRbeta, and RXRgamma). 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 RXRgamma) 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 RXRalpha and RARalpha was frequently observed. In contrast, RXRbeta expression decreased in 18% of the tumor specimens. Furthermore, there was a marked decrease in the expression of RARbeta in 63% of the tumors (P<.0001). Decreased expression of RARgamma 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 RARalpha and RXRalpha is either normal or elevated in NSCLC. In contrast, a large percentage of tumors show a marked decrease in the expression of RARbeta, RARgamma, and RXRbeta 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.
Insights
Altered retinoid receptor expression, including decreased RARbeta, RARgamma, and RXRbeta, is common in non-small-cell lung cancer (NSCLC). These changes, along with LOH at 3p24, suggest a role for retinoid receptors in lung carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Retinoids inhibit carcinogenesis in pre-cancerous lesions and reduce second primary lung cancer risk.
- Retinoid effects are mediated by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).
Purpose of the Study:
- To investigate in vivo retinoid receptor expression abnormalities in non-small-cell lung cancer (NSCLC).
Main Methods:
- Immunohistochemistry and in situ hybridization were used to analyze retinoid receptor expression in paired normal and tumor lung tissues from 76 NSCLC patients.
- Reverse transcription-polymerase chain reaction (RT-PCR) assessed RAR messenger RNA levels.
- Loss of heterozygosity (LOH) at chromosome 3p24 was analyzed.
Main Results:
- Overexpression of RXRalpha and RARalpha was frequent in NSCLC tumors.
- Decreased expression of RXRbeta (18%), RARbeta (63%), and RARgamma (41%) was observed in tumor specimens.
- Loss of heterozygosity (LOH) at chromosome 3p24 occurred in 41% of tumors.
Conclusions:
- NSCLC exhibits altered retinoid receptor expression, with decreased RARbeta, RARgamma, and RXRbeta being prominent.
- High frequency of LOH at 3p24 was noted in both tumors and non-neoplastic lesions.
- These findings suggest that dysregulated retinoid receptor expression may contribute to lung carcinogenesis.