Angiotensin II activates MAP kinase and NF-kappaB through angiotensin II type I receptor in human pancreatic cancer cells

Int J Oncol. 2004 Oct;25(4):849-56.

Abstract

Pancreatic ductal cancer has higher angiotensin II concentrations compared with normal pancreas or other solid tumors. This study examined angiotensin II type 1 (AT1) receptor expression and the role of angiotensin II in proliferation and survival of human pancreatic cancer cells. All three pancreatic cancer cell lines studied, from well to poorly-differentiated types, HPAF-II, AsPC-1, and Panc-1, showed strong expression of AT1 receptor. In contrast, HT-29 human colon cancer cells showed extremely weak expression. Angiotensin II stimulated the growth of pancreatic cancer cells through MAP kinase activation but had no significant effect on proliferation of HT-29 colon cancer cells. In addition, angiotensin II significantly prevented cisplatin (CDDP)-induced apoptosis through NF-kappaB activation and the subsequent production of anti-apoptotic molecules, including survivin and Bcl-XL, in pancreatic cancer cells. These findings suggest that angiotensin II plays a role in the growth and chemoresistance of AT1-positive pancreatic cancer cells through its action as a potent mitogen and anti-apoptotic molecule.

MeSH terms

  • Aged
  • Angiotensin II / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Neoplasm Proteins
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Receptor, Angiotensin, Type 1 / physiology*
  • Signal Transduction
  • Survivin
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor, Angiotensin, Type 1
  • Survivin
  • bcl-X Protein
  • Angiotensin II
  • Mitogen-Activated Protein Kinases