Thymosin Beta 4 is overexpressed in human pancreatic cancer cells and stimulates proinflammatory cytokine secretion and JNK activation

Cancer Biol Ther. 2008 Mar;7(3):419-23. doi: 10.4161/cbt.7.3.5415. Epub 2007 Dec 13.

Abstract

Background: Thymosin beta 4 (T beta 4) has been shown to be associated with tumor metastasis and angiogenesis; however, its role in pancreatic cancer has not been understood. In the current study, we examined the expression of T beta 4 in pancreatic cancer cells, and determined the effect of exogenous T beta 4 on cytokine secretion, and signal transduction in human pancreatic cancer cells.

Results: Pancreatic cancer cell lines expressed higher amount of T beta 4 mRNA than normal human pancreatic ductal epithelium (HPDE) cells. Exogenous T beta 4 increased the secretion of proinflammatory cytokines IL-6, IL-8 and MCP-1 in Panc-1 cells. In addition, T beta 4 activated Jun N-terminal Kinase (JNK) signaling pathways in pancreatic cancer cells.

Methods: The mRNA levels of T beta 4 were determined by real-time RT PCR. Phosphorylation of JNK in pancreatic cancer cells was determined using Bio-Plex phosphoprotein assay. The expression of cytokines in human pancreatic cancer cell lines was determined with Bio-Plex cytokine assay.

Conclusions: T beta 4 might be involved in stimulating human pancreatic cancer progression by promoting proinflammatory cytokine environment and activating JNK signaling pathway. Targeting T beta 4 and related molecules may be a novel therapeutic strategy for pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / physiopathology
  • Cytokines / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inflammation / physiopathology*
  • Kinetics
  • MAP Kinase Kinase 4 / metabolism*
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / physiopathology
  • Phosphorylation
  • Thymosin / genetics*

Substances

  • Cytokines
  • thymosin beta(4)
  • Thymosin
  • MAP Kinase Kinase 4