MYB regulates the DNA damage response and components of the homology-directed repair pathway in human estrogen receptor-positive breast cancer cells.

Abstract:

:Over 70% of human breast cancers are estrogen receptor-positive (ER+), most of which express MYB. In these and other cell types, the MYB transcription factor regulates the expression of many genes involved in cell proliferation, differentiation, tumorigenesis, and apoptosis. So far, no clear link has been established between MYB and the DNA damage response in breast cancer. Here, we found that silencing MYB in the ER+ breast cancer cell line MCF-7 led to increased DNA damage accumulation, as marked by increased γ-H2AX foci following induction of double-stranded breaks. We further found that this was likely mediated by decreased homologous recombination-mediated repair (HRR), since silencing MYB impaired the formation of RAD51 foci in response to DNA damage. Moreover, cells depleted for MYB exhibited reduced expression of several key genes involved in HRR including BRCA1, PALB2, and TOPBP1. Taken together, these data imply that MYB and its targets play an important role in the response of ER+ breast cancer cells to DNA damage, and suggest that induction of DNA damage along with inhibition of MYB activity could offer therapeutic benefits for ER+ breast cancer and possibly other cancer types.

journal_name

Oncogene

journal_title

Oncogene

authors

Yang RM,Nanayakkara D,Kalimutho M,Mitra P,Khanna KK,Dray E,Gonda TJ

doi

10.1038/s41388-019-0789-3

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

5239-5249

issue

26

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-019-0789-3

journal_volume

38

pub_type

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