Protein Kinase C Delta restrains growth in ACTH-secreting pituitary adenoma cells

Mol Cell Endocrinol. 2016 Jan 5:419:252-8. doi: 10.1016/j.mce.2015.10.025. Epub 2015 Oct 30.

Abstract

Protein Kinase C Delta (PRKCD) has been highlighted among disrupted pathways in corticotroph adenomas. PRKCD is expressed at low level in human corticotroph adenomas and controls cell cycle in vitro. Therefore, PRKCD may play an important role in the development/progression of corticotroph adenomas, warranting further studies to understand the role of PRKCD and related pathways in restraining pituitary cell growth. We evaluated PRKCD role in influencing cell behavior in terms of cell viability, hormone expression and protein expression profile, by silencing PRKCD in AtT-20/D16v-F2 cells. PRKCD silencing increases cell viability, enhances hormone expression and induces morphological changes associated with deregulation of adhesion molecules. PRKCD silencing is associated with an increase in Epithelial Growth Factor Receptor (EGFR) expression, a marker of tumor aggressive behavior, and sensitivity to anti-EGFR molecules. PRKCD might restrain corticotroph adenoma cells from acquiring an aggressive behavior, candidating PRKCD as a possible molecular target for the treatment of corticotroph adenomas.

Keywords: ACTH; Epithelial growth factor receptor; Pituitary; Protein Kinase C Delta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Pituitary Neoplasms / metabolism*
  • Pro-Opiomelanocortin / metabolism
  • Protein Kinase C-delta / metabolism*

Substances

  • Pro-Opiomelanocortin
  • Adrenocorticotropic Hormone
  • Prkcd protein, mouse
  • EGFR protein, human
  • ErbB Receptors
  • PRKCD protein, human
  • Protein Kinase C-delta