Estrogen receptor positive breast tumors resist chemotherapy by the overexpression of P53 in Cancer Stem Cells

Abstract

Background and objectives: Breast cancer (BC) is classified according to estrogen receptor (ER) status into ER⁺ and ER^- tumors. ER⁺ tumors have a worse response to chemotherapy compared to ER^- tumors. BCL-2, TP53, BAX and NF-ΚB are involved in drug resistance in the ER⁺ tumors. Recently it was shown that Cancer Stem Cells (CSCs) play an important role in drug resistance. In this study we tested the hypothesis that CSCs of the ER⁺ tumors resist drug through the overexpression of BCL-2, TP53, BAX and NF-ΚB.

Methods: CSCs were isolated by anoikis resistance assay from MCF7 (ER⁺) and MDA-MB-231 (ER^-) cell lines. Isolated CSCs were treated with doxorubicin (DOX) and the mRNA expression levels of BCL-2, TP53, BAX and NFKB were investigated by quantitative real time PCR (qPCR) with and without treatment.

Results: BCL-2, BAX and NF-ΚB showed decreased expression in MCF7 bulk cancer cells after DOX treatment whereas only BCL-2 and BAX showed decreased expression in MDA-MB-231 bulk cancer cells. Interestingly TP53 was the only gene showed a considerable increase in its expression in CSCs of the ER⁺ MCF7 cell line compared to bulk cancer cells. Moreover, TP53 was the only gene showing exceptionally higher level of expression in MCF7-CSCs compared to MDA-MB-231-CSCs.

Conclusion: Our results suggest that CSCs in the ER⁺ cells escape the effect of DOX treatment by the elevation of p53 expression.

Keywords: Breast cancer; Cancer Stem Cells; Drug resistance; Estrogen receptors.