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Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
07:03

Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples

Published on: October 2, 2020

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PRMT5 determines the sensitivity to chemotherapeutics by governing stemness in breast cancer

Zhe Wang1, Jing Kong1, Ying Wu1

  • 1Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.

Breast Cancer Research and Treatment
|November 30, 2017
PubMed
Abstract

Insights

Protein arginine methyltransferase 5 (PRMT5) drives breast cancer stemness and doxorubicin resistance by regulating key stemness factors. Targeting PRMT5 may overcome chemotherapy resistance in breast cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Acquired resistance to chemotherapy is a significant clinical problem in breast cancer treatment.
  • Cancer stem cells are implicated in drug resistance, with protein arginine methyltransferase 5 (PRMT5) identified as crucial for maintaining stemness.
  • The precise role of PRMT5 in breast cancer stemness and drug resistance remains unclear.

Purpose of the Study:

  • To investigate the impact of PRMT5 on breast cancer cell stemness.
  • To determine the effect of PRMT5 on sensitivity to doxorubicin, a common chemotherapeutic agent.
  • To elucidate the regulatory mechanisms by which PRMT5 influences stemness and drug resistance.

Main Methods:

  • Assessed PRMT5 expression across various breast cancer cell lines and normal epithelial cells.
  • Utilized shRNA for PRMT5 knockdown and stable overexpression of wild-type and mutant PRMT5.
  • Evaluated doxorubicin sensitivity using MTT assays, TUNEL assays, and Western blot analysis.
  • Assessed cell stemness through CD24/CD44 cell sorting and mammosphere formation assays.

Main Results:

  • PRMT5 expression was analyzed in multiple breast cancer cell lines.
  • PRMT5 was found to regulate stemness factors OCT4/A, KLF4, and C-MYC.
  • PRMT5 significantly affects breast cancer cell resistance to doxorubicin.

Conclusions:

  • PRMT5 plays a critical role in governing breast cancer cell stemness.
  • PRMT5 influences the development of doxorubicin resistance in breast cancer.
  • Targeting PRMT5 may represent a therapeutic strategy to overcome chemotherapy resistance in breast cancer.
Keywords:
Breast cancerCancer stem cellDoxorubicin resistancePRMT5

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