雌激素受体阳性乳腺肿瘤通过癌干细胞中P53的过表达来抵抗化疗。
Estrogen receptor positive breast tumors resist chemotherapy by the overexpression of P53 in Cancer Stem Cells.
作者信息
Ashour Fatma, Awwad Mohammed H, Sharawy Hayam E L, Kamal Mohamed
机构信息
Department of Zoology, Faculty of Science, University of Benha, Benha, Egypt.
Department of Zoology, Faculty of Science, University of Benha, Benha, Egypt.
出版信息
J Egypt Natl Canc Inst. 2018 Jun;30(2):45-48. doi: 10.1016/j.jnci.2018.04.002. Epub 2018 May 17.
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.
背景与目的
乳腺癌（BC）根据雌激素受体（ER）状态分为ER⁺和ER⁻肿瘤。与ER⁺肿瘤相比，ER⁻肿瘤对化疗的反应较差。BCL-2、TP53、BAX和NF-ΚB参与ER⁻肿瘤的耐药性。最近研究表明，癌症干细胞（CSCs）在耐药性中起重要作用。在本研究中，我们检验了以下假设：ER⁻肿瘤的CSCs通过BCL-2、TP53、BAX和NF-ΚB的过表达来抵抗药物。
方法
通过失巢凋亡抗性试验从MCF7（ER⁺）和MDA-MB-231（ER⁻）细胞系中分离CSCs。将分离出的CSCs用阿霉素（DOX）处理，通过定量实时PCR（qPCR）研究处理和未处理情况下BCL-2、TP53、BAX和NFKB的mRNA表达水平。
结果
DOX处理后，MCF7原代癌细胞中BCL-2、BAX和NF-ΚB表达降低，而MDA-MB-231原代癌细胞中只有BCL-2和BAX表达降低。有趣的是，与原代癌细胞相比，TP53是ER⁺MCF7细胞系CSCs中唯一表达显著增加的基因。此外，与MDA-MB-231-CSCs相比，TP53是在MCF7-CSCs中表达水平异常高的唯一基因。
结论
我们的结果表明，ER⁻细胞中的CSCs通过p53表达的升高逃避DOX治疗的影响。
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