Retinoid and retinoid X nuclear receptor subtypes in human thyroid papillary carcinoma, breast cancer and renal carcinomas: mRNA expression pattern


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Julius Brtko1,Lucia Bialesova1,Vladimir Lenko2,Stefan Galbavy3,Jan Podoba3,Dana Macejova1
1Institute of Experimental Endocrinology, BMC, Slovak Academy of Sciences, Bratislava,2University Hospital, Bratislava,3Saint Elizabeth Institute of Oncology, Bratislava

Abstract

Background

Nuclear retinoid receptors (RARs) upon a ligand binding act as all-trans retinoic acid-inducible transcription factors interacting as conditional heterodimers with nuclear retinoid X (rexinoid) receptors (RXRs). The disruption of retinoic acid (RA) signalling pathways is believed to underlie the etiology of a number of malignancies. RAR and RXR ligands are known to play role in reprogramming several tumour cells, and thus the development of appropriate ligands with reduced teratogenic and other side effects are still highly required. In this study, we have investigated expression pattern of retinoid receptor subtypes (RARalpha, RARbeta, RARgamma) and retinoid X nuclear receptor subtypes (RXRalpha, RXRbeta, RXRgamma) in three different human organ malignancies, i) thyroid papillary carcinoma, ii) breast cancer, and iii) renal carcinoma.

Method

26 samples of thyroid papillary carcinoma, more than 130 breast cancer samples, and over 100 samples of renal carcinoma have been analyzed. The expression pattern of the retinoid/rexinoid nuclear receptor subtypes has been evaluated by the RT-PCR techniques.

Results

Significantly increased expression of RARalpha and RARgamma in overall group of thyroid papillary carcinoma patients was demonstrated. In breast cancer, the expression of respective RAR subtypes was in the following order: RARalpha > RARbeta > RARgamma. Among RXR subtypes, only RXRgamma was markedly diminished in breast cancer tissue. In renal carcinomas, expression of RARalpha and RARbeta was higher when compared to intact kidney tissue. Expression of RARgamma was found to be markedly decreased in all renal tumours that were found to express RXRalpha and RXRbeta. Expression of RXRgamma was markedly lower in renal carcinomas when compared to intact renal tissue.

Conclusion

We clearly demon­strate differences in RAR and RXR subtype mRNA expression patterns in selected human cancer tissues as studied by RT-PCR. These findings offer possibilities for exploitation in clinical oncology, predominantly in the differential diagnosis and treatment. Supported by APVV-15-0372 and VEGA 2/0171/17 grants.