Expression of mRNA coding for TGF-beta and its receptors in irradiated human breast carcinoma MCF-7 cells differing in their sensitivity to doxorubicin.
AIM: The effect of X-irradiation on the expression of mRNAs coding for transforming growth factor beta (TGF-beta) and its receptors was compared in human breast carcinoma MCF-7 cells differing in their sensitivity to doxorubicin. METHODS: Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the estimation of mRNAs expression for TGF-beta1, TGF-beta2 and TGF-beta type I and II receptors in the unirradiated and irradiated cells of two sublines of MCF-7 cells--sensitive (MCF-7(wt)) and resistant (MCF-7(DOX/R)) to doxorubicin. RESULTS: X-irradiation caused an increase in TGF-beta1 coding for mRNA expression in both breast cancer cell lines tested and an elevation of TGF-beta2 mRNA expression in doxorubicin-resistant subline. The down-regulation of TGF-beta type I and II receptors in the irradiated MCF-7(DOX/R) cells was revealed at the transcriptional level. CONCLUSIONS: The results of our study show that the development of refractoriness of used tumor cells to anti-cancer drug doxorubicin, at least partly, can be caused by the impairment in TGF-beta signaling pathway.