The interplay between estrogen receptor beta and protein kinase C, a crucial collaboration for medulloblastoma cell proliferation and invasion

Cell Signal. 2022 Apr:92:110246. doi: 10.1016/j.cellsig.2022.110246. Epub 2022 Jan 13.

Abstract

Medulloblastoma (MB) is the most common and aggressive pediatric intracranial tumor. Estrogen receptor β (ERβ) expression correlates with MB development and its phosphorylation modifies its transcriptional activity in a ligand-dependent or independent manner. Using in silico tools, we have identified several residues in ERβ protein as potential targets of protein kinases C (PKCs) α and δ. Using Daoy cells, we observed that PKCα and PKCδ associate with ERβ and induce its phosphorylation. The activation of ERβ promotes MB cells proliferation and invasion, and PKCs downregulation dysregulates these steroid receptor mediated processes. Our data suggest that these kinases may play a crucial role in the regulation of the ERβ transcriptional activity. Overexpression of both PKCα and PKCδ in MB biopsies samples supports their relevance in MB progression.

Keywords: Estrogen receptor β; Medulloblastoma; Protein kinase C α; Protein kinase C δ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Cerebellar Neoplasms*
  • Child
  • Estrogen Receptor alpha
  • Estrogen Receptor beta* / genetics
  • Estrogen Receptor beta* / metabolism
  • Humans
  • Medulloblastoma* / genetics
  • Medulloblastoma* / metabolism
  • Protein Kinase C*
  • Protein Kinase C-alpha / metabolism*
  • Protein Kinase C-delta / metabolism*

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Protein Kinase C-delta