Protein ISGylation and free ISG15 levels are increased by interferon gamma in breast cancer cells

Biochem Biophys Res Commun. 2018 May 23;499(4):973-978. doi: 10.1016/j.bbrc.2018.04.030. Epub 2018 Apr 9.

Abstract

The induction of ISG15 by interferon (IFN)-α/β and subsequent protein ISGylation has been demonstrated in several cell types. However, regulation of free ISG15 levels and ISGylation by other IFNs and its implications in some carcinomas have not yet been completely evaluated. Here, we demonstrated that free ISG15 and ISGylation levels are enhanced by IFN-γ treatment in the estrogen receptor-α-positive and -negative breast cancer cells, MCF-7 and MDA-MB-231, respectively. Specifically, IFN-γ increases free ISG15 levels in the cytoplasm and ISGylation in the nucleus and cytoplasm, but in a manner distinct between MCF-7 and MDA-MB-231 cells. Therefore, free ISG15 and ISGylation may play central roles in mammary tumors by differentially modulating certain tumorigenic characteristics of estrogen receptor-α-positive and -negative breast cancer cells.

Keywords: Breast cancer; ERα; IFN-γ; ISG15; ISGylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interferon-gamma / pharmacology*
  • Protein Transport / drug effects
  • Subcellular Fractions / metabolism
  • Ubiquitins / genetics
  • Ubiquitins / metabolism*

Substances

  • Cytokines
  • Estrogen Receptor alpha
  • Ubiquitins
  • ISG15 protein, human
  • Interferon-gamma