p8 inhibits the growth of human pancreatic cancer cells and its expression is induced through pathways involved in growth inhibition and repressed by factors promoting cell growth

Mol Cancer. 2003 Nov 5;2:37. doi: 10.1186/1476-4598-2-37.

Abstract

Background: p8 is a stress-induced protein with multiple functions and biochemically related to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in pancreatic cancer-derived cells.

Methods: Expression of p8 was silenced in the human pancreatic cancer cell lines Panc-1 and BxPc-3 by infection with a retrovirus expressing p8 RNA in the antisense orientation. Cell growth was measured in control and p8-silenced cells. Influence on p8 expression of the induction of intracellular pathways promoting cellular growth or growth arrest was monitored.

Results: p8-silenced cells grew more rapidly than control cells transfected with the empty retrovirus. Activation of the Ras-->Raf-->MEK-->ERK and JNK intracellular pathways down-regulated p8 expression. In addition, the MEK1/2 inhibitor U0126 and the JNK inhibitor SP600125 up-regulates expression of p8. Conversely, p38 or TGFbeta-1 induced p8 expression whereas the specific p38 inhibitor SB203580 down-regulated p8 expression. Finally, TGFbeta-1 induction was in part mediated through p38.

Conclusions: p8 inhibits the growth of human pancreatic cancer cells. p8 expression is induced through pathways involved in growth inhibition and repressed by factors that promote cell growth. These results suggest that p8 belongs to a pathway regulating the growth of pancreatic cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Basic Helix-Loop-Helix Transcription Factors
  • Butadienes / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Culture Media / chemistry
  • Culture Media / pharmacology
  • Culture Media, Serum-Free / pharmacology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Silencing
  • Genetic Vectors / genetics
  • Growth Inhibitors / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Nitriles / pharmacology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-raf / metabolism
  • Pyridines / pharmacology
  • RNA, Antisense / genetics
  • Retroviridae / genetics
  • Transfection
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • ras Proteins / metabolism

Substances

  • Anthracenes
  • Basic Helix-Loop-Helix Transcription Factors
  • Butadienes
  • Culture Media
  • Culture Media, Serum-Free
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Growth Inhibitors
  • Imidazoles
  • NUPR1 protein, human
  • Neoplasm Proteins
  • Nitriles
  • Pyridines
  • RNA, Antisense
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • U 0126
  • pyrazolanthrone
  • Proto-Oncogene Proteins c-raf
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • ras Proteins
  • SB 203580