Resistance of breast cancer cells to all-trans retinoic acid is associated with a decrease in the basal level of nuclear receptor RARα expression and induction of cytochrome CYP26A1 and CYP26B1 expression

Introduction. Retinoic acid (RA) is a key regulator of cell differentiation and a critical player in such systemic processes in the body as embryonic development, immune system cell maturation and functioning, tissue remodeling and several others. This compound displays an antitumor activity due to its ability to stimulate differentiation, induce apoptosis  and inhibit proliferation of malignant cells. The rapid acquisition of resistance to RA and its analogues by solid tumor cells is one of the main problems limiting the widespread use of retinoids in the therapy of malignant neoplasms. The mechanisms of RA-resistance are still poorly understood.

The study objective – assessment of the relationship between the basal expression level of the nuclear RARα receptor and the RA-induced expression of the cytochromes CYP26A1and CYP26B1 with the resistance of breast cancer cells to the action of all-trans-retinoic acid.

Materials and methods. Cell lines were cultured, the sensitivity of breast cancer cells to the action of fully trans-retinoic acid, RNA isolation, reverse transcription reaction and real-time polymerase chain reaction were analyzed).

Results. In present study, using an experimental model represented by 9 breast cancer cell lines with different level of sensitivity to RA, we showed that the expression of the RA nuclear receptor RARα, as well as the level of mRNA induction of CYP26A1 and CYP26B1 cytochromes in response to RA treatment correlate with RA-sensitivity.

Conclusion. Thus, a decrease of RARα expression as well as the reduced ability to catabolize RA are factors associated with RA-resistance of breast cancer cells.

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