Thymosinalpha1 stimulates cell proliferation by activating ERK1/2, JNK, and increasing cytokine secretion in human pancreatic cancer cells

Cancer Lett. 2007 Apr 8;248(1):58-67. doi: 10.1016/j.canlet.2006.05.019. Epub 2006 Jul 7.

Abstract

In this study, we investigated the expression and function of thymosinalpha1 (Thyalpha1) in human pancreatic cancer. We found that human pancreatic cancer cell lines Panc-1, Panc03.27, ASPC-1, and PL45 cells significantly over-expressed the mRNA of Thyalpha1 as compared to the normal human pancreatic ductal epithelium (HPDE) cells.. Thyalpha1 mRNA and protein levels were also over-expressed in clinical pancreatic adenocarcinoma specimens. In addition, synthetic Thyalpha1 significantly promoted Panc-1 cell proliferation and increased phosphorylation of ERK1/2 and JNK. Furthermore, Thyalpha1 increased the secretion of multiple cytokines including IL-10, IL-13, and IL-17 in Panc-1 cells. Thus, Thyalpha1 may have a new role in pancreatic cancer pathogenesis.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Interleukin-10 / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-17 / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th2 Cells / metabolism
  • Thymalfasin
  • Thymosin / analogs & derivatives*
  • Thymosin / genetics
  • Thymosin / metabolism
  • Thymosin / pharmacology

Substances

  • Cytokines
  • Interleukin-13
  • Interleukin-17
  • RNA, Messenger
  • Interleukin-10
  • Thymosin
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Thymalfasin