title: Insulin-like growth factor II activates mitogenic signaling in pancreatic cancer cells via IRS-1.
abstract: Insulin-like growth factor-II (IGF-II) action and expression were examined in 3 human pancreatic cancer cell lines. IGF-II expression was also studied in 17 normal and 12 malignant pancreatic tissues. IGF-II enhanced the growth of all 3 cell lines. In COLO-357 and PANC-1 cells, one-half maximal stimulation occurred at 0.3 and 0.4 nM IGF-II, respectively. In ASPC-1 cells, one-half maximal stimulation occurred at 0.9 nM IGF-II. A monoclonal antibody (alpha IR3) that blocks ligand binding to the insulin-like growth factor I (IGF-I) receptor (IGF-IR) inhibited IGF-II-mediated growth stimulation, and IGF-II enhanced insulin-receptor substrate 1 (IRS-1) phosphorylation. IGF-II mRNA transcripts were present in COLO-357 cells, in 4 of 17 normal human pancreatic tissues, and in 8 of the 12 cancer samples. By immunohistochemistry, IGF-II was present in the islets of both normal and malignant pancreatic tissues, and occasionally in the cancer cells within the tumor mass. These findings indicate that IGF-II acts via IGF-IR to enhance mitogenic signaling in pancreatic cancer cells and suggest that islet-derived IGF-II may contribute to pancreatic cancer cell growth in vivo.
authors.affiliation: UNIV CALIF IRVINE,DIV ENDOCRINOL DIABET & METAB,IRVINE,CA 92717. UNIV ULM,DEPT GEN SURG,D-89075 ULM,GERMANY.
authors.forename: U
authors.initials: U
authors.lastname: Bergmann
authors.forename: H
authors.initials: H
authors.lastname: Funatomi
authors.forename: M
authors.initials: M
authors.lastname: Kornmann
authors.forename: T
authors.initials: T
authors.lastname: Ishiwata
authors.forename: H
authors.initials: H
authors.lastname: Beger
authors.forename: M
authors.initials: M
authors.lastname: Korc