A novel group of genes that cause endocrine resistance in breast cancer identified by dynamic gene expression analysis

Oncotarget. 2022 Apr 6;13:600-613. doi: 10.18632/oncotarget.28225. eCollection 2022.

Abstract

Breast cancer (BC) is the most common type of cancer diagnosed in women. Among female cancer deaths, BC is the second leading cause of death worldwide. For estrogen receptor-positive (ER-positive) breast cancers, endocrine therapy is an effective therapeutic approach. However, in many cases, an ER-positive tumor becomes unresponsive to endocrine therapy, and tumor regrowth occurs after treatment. While some genetic mutations contribute to resistance in some patients, the underlying causes of resistance to endocrine therapy are mostly undetermined. In this study, we utilized a recently developed statistical approach to investigate the dynamic behavior of gene expression during the development of endocrine resistance and identified a novel group of genes whose time course expression significantly change during cell modelling of endocrine resistant BC development. Expression of a subset of these genes was also differentially expressed in microarray analysis of endocrine-resistant and endocrine-sensitive tumor samples. Surprisingly, a subset of those genes was also differentially genes expressed in triple-negative breast cancer (TNBC) as compared with ER-positive BC. The findings suggest shared genetic mechanisms may underlie the development of endocrine resistant BC and TNBC. Our findings identify 34 novel genes for further study as potential therapeutic targets for treatment of endocrine-resistant BC and TNBC.

Keywords: breast cancer; endocrine resistance; gene clustering; gene expression profiling; triple negative breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Drug Resistance, Neoplasm / genetics
  • Endocrine Gland Neoplasms* / genetics
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Triple Negative Breast Neoplasms* / genetics

Substances

  • Receptors, Estrogen