Endocrine Abstracts

Introduction: Nuclear retinoid receptors (RARs) upon a ligand binding act as all-trans retinoic acid-inducible transcription factors interacting as 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. Retinoids – cell differentiation agents that may ‘reprogram’ tumours, i.e. retinoic acid derivatives or retinoic acid related compounds with reduced teratogenic and other side effects are still highly required. In this study, we have investigated expression pattern of retinoid receptor subtypes (RARα, RARβ, RARγ) and rexinoid nuclear receptor subtypes (RXRα, RXRβ, RXRγ) in three different organ malignancies, i) thyroid different carcinoma tissues, ii) breast cancer, and iii) renal cancer tissues.

Description of methods/design: Approximately 40 samples of different types of thyroid carcinoma, more than 150 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 RARα and RARγ in overall group of papillary carcinoma patients was demonstrated. In breast cancer, the expression of respective RAR subtypes was in the following order: RARα >RARβ >RARγ. Among RXR subtypes, only RXRγ was significantly diminished in breast cancer tissue. In renal carcinomas, expression of RARα and RARβ was higher when compared to intact kidney tissue. Expression of RARγ was found to be markedly decreased in all renal tumours. All renal tumours were capable to express RXRα and RXRβ. Expression of RXRγ was significantly lower in comparison with intact renal tissue.

Conclusion: The molecular mechanisms demonstrating differences in RAR and RXR subtype mRNA expression patterns in thyroid carcinomas, breast and renal cancer may find exploitation in clinical oncology, predominantly, in the differential diagnosis of different organ neoplasms.

Disclosure: Supported by the grant APVV-0160-11, the VEGA grant 2/0171/14, and the Centre of Excellence CEMAN grant.