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

Journal of the Egyptian National Cancer Institute
Fatma AshourMohamed Kamal

Abstract

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. 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. 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. Our results sugg...Continue Reading

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