Estradiol and tamoxifen differently affects the inhibitory effects of vitamin A and their metabolites on the proliferation and expression of α2β1 integrins in MCF-7 breast cancer cells

Retinoids are well known inhibitors of estrogen-dependent breast cancer cell growth and differentiation. alpha2beta1 integrins are involved in the normal growth and differentiation of breast cells, they also take part in many pathological processes including malignancies. The aim of the study was to evaluate the effect of estradiol and tamoxifen on the inhibitory action of retinoids on the proliferation of MCF-7 breast cancer cells and alpha2beta1 integrin expression.Evaluation was based on [3H]thymidine incorporation and the proliferative activity of PCNA- and Ki 67-positive cells. Expression of alpha2beta1 was assessed through immunocytochemical analysis.Treatment of cancer cells with the examined compounds and tamoxifen (10 microM) revealed that only 13-cis retinoic acid (13-cis RA) and all-trans retinoic acid (ATRA) (10(-5) M) decreased cells proliferation compared to the tamoxifen group (30.84%+/-3.32, p<0.01 and 31.05%+/-4.67, p<0.01, respectively). The lowest fraction of PCNA positive cells was also observed after the simultaneous addition ATRA (10(-5) M) and tamoxifen (10 microM) (30.75%+/-0.95, p<0.01, compared to the tamoxifen group). Our results showed that the decrease of alpha2beta1 integrin expression by 13-cis RA (10(-5) M, 49.6+/-3.25%) and ATRA (10-9 M, 15.0%+/-5.0) was augmented by tamoxifen and to a lesser extent by estradiol, particularly in the case of ATRA at 10(-7) or 10(-9) M.This data suggest that tamoxifen augments the inhibitory effect of retinoids on proliferation and alpha2beta1 integrin expression in MCF-7 cells.