Knockdown of glucose-regulated protein 78 enhances poly(ADP-ribose) polymerase cleavage in human pancreatic cancer cells exposed to endoplasmic reticulum stress

Oncol Rep. 2014 Dec;32(6):2343-8. doi: 10.3892/or.2014.3533. Epub 2014 Oct 6.

Abstract

The present study examined the expression of glucose‑regulated protein 78 (GRP78/Bip) in human pancreatic cancer cell lines and the effect of knockdown of GRP78 on the cleavage of poly(ADP-ribose) polymerase (PARP). Human pancreatic cancer cell lines (KP-2, MIAPaCa-2, Panc-1 and SUIT-2), constitutively expressed GRP78. We also demonstrated that ER stress induced by thapsigargin upregulated protein levels of GRP78. In the presence of thapsigargin, knockdown of GRP78 enhanced the PARP cleavage in the human pancreatic cancer cells. These results provide evidence that GRP78 is a potential therapeutic target for 'difficult-to-treat' pancreatic cancer, in which ER stress signaling in part falls into disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 4 / genetics
  • Activating Transcription Factor 4 / metabolism
  • Activating Transcription Factor 6 / genetics
  • Activating Transcription Factor 6 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress*
  • Eukaryotic Initiation Factor-2 / metabolism
  • Gene Expression
  • Gene Knockdown Techniques
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Pancreatic Neoplasms
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Phosphatase 1 / genetics
  • Protein Phosphatase 1 / metabolism
  • Protein Processing, Post-Translational / drug effects
  • Proteolysis
  • Regulatory Factor X Transcription Factors
  • Thapsigargin / pharmacology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ATF4 protein, human
  • ATF6 protein, human
  • Activating Transcription Factor 6
  • DNA-Binding Proteins
  • Endoplasmic Reticulum Chaperone BiP
  • Eukaryotic Initiation Factor-2
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • Activating Transcription Factor 4
  • Thapsigargin
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • PPP1R15A protein, human
  • Protein Phosphatase 1