Novel estrogen-responsive genes (ERGs) for the evaluation of estrogenic activity

PLoS One. 2022 Aug 17;17(8):e0273164. doi: 10.1371/journal.pone.0273164. eCollection 2022.

Abstract

Estrogen action is mediated by various genes, including estrogen-responsive genes (ERGs). ERGs have been used as reporter-genes and markers for gene expression. Gene expression profiling using a set of ERGs has been used to examine statistically reliable transcriptomic assays such as DNA microarray assays and RNA sequencing (RNA-seq). However, the quality of ERGs has not been extensively examined. Here, we obtained a set of 300 ERGs that were newly identified by six sets of RNA-seq data from estrogen-treated and control human breast cancer MCF-7 cells. The ERGs exhibited statistical stability, which was based on the coefficient of variation (CV) analysis, correlation analysis, and examination of the functional association with estrogen action using database searches. A set of the top 30 genes based on CV ranking were further evaluated quantitatively by RT-PCR and qualitatively by a functional analysis using the GO and KEGG databases and by a mechanistic analysis to classify ERα/β-dependent or ER-independent types of transcriptional regulation. The 30 ERGs were characterized according to (1) the enzymes, such as metabolic enzymes, proteases, and protein kinases, (2) the genes with specific cell functions, such as cell-signaling mediators, tumor-suppressors, and the roles in breast cancer, (3) the association with transcriptional regulation, and (4) estrogen-responsiveness. Therefore, the ERGs identified here represent various cell functions and cell signaling pathways, including estrogen signaling, and thus, may be useful to evaluate estrogenic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Cell Line, Tumor
  • Estrogen Receptor alpha / metabolism
  • Estrogens / metabolism
  • Estrogens / pharmacology
  • Estrone
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • Transcriptional Regulator ERG / genetics

Substances

  • ERG protein, human
  • Estrogen Receptor alpha
  • Estrogens
  • Transcriptional Regulator ERG
  • Estrone

Grant support

This study was supported partly by a grant from Kyushu Sangyo University for promoting basic technologies, and a Grant-in-Aid for Basic Areas (Kakenhi 20H04343) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.