Novel synergistic antitumour properties of nuclear retinoid X receptor (RXR) agonists as a consequence of the conditional RXR-RAR heterodimer formation in human breast cancer cells       

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Principal investigator: Július Brtko
Principal investigator (IMPG SAS): Zdena Sulova

Duration: July 2016 – June 2020
Coordinating institution: Institute of Experimental Endocrinology BMC SAS


Nuclear retinoid X receptors (RXR) are considered to be important target molecules for treatment of several malignant diseases. Characteristic feature of RXR agonists is their capability to amplify the effect of endogenous ligand of nuclear retinoid receptors (RAR). The objective of the project proposal is the investigation of novel antitumour properties of the biologically active agonists of nuclear retinoid X receptors, which upon binding to RXR molecule function with the “partner” RAR receptors in the presence of all-trans retinoic acid as a “conditional” heterodimer. The object of investigation is a selected group of retinoid X receptors agonists of natural or synthetic origin. For a number of experiments, we will employ two different human breast cancer cell lines (estrogen receptor positive and estrogen receptor negative) in order to find cooperative effects of RXR agonist and RAR ligand at the RXR-RAR heterodimer leading to enhanced tumour cell growth inhibition or induction of apoptosis. The parallel objective of the project is investigation of the effects of the “supramolecular ligand/agonist” formation from a group of RXR agonists of natural or synthetic origin. We expect a number of original results yielding from experimental work that should contribute to the development of novel therapeutical potentialities for breast cancer treatment.