Estrogen receptor positive breast tumors resist chemotherapy by the overexpression of P53 in cancer stem cells

Abstract EN

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