Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer

Marko Kornmann, Haruhisa Maruyama, Uwe Bergmann, Pam Tangvoranuntakul, Hans G. Beger, Morris F. White, Murray Korc

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Insulin receptor substrate-2 (IRS-2) is a multisite docking protein implicated in mitogenic signaling after activation of the insulin and insulin-like growth factor (IGF)-I receptors. In the present study, we characterized IRS-2 expression and function in human pancreatic cancer. IRS- 2 mRNA and protein were expressed in ASPC-1 and COLO-357 human pancreatic cancer cell lines. Insulin, IGF-I, and IGF-II enhanced the growth of both cell lines, stimulated tyrosine phosphorylation of IRS-2, and increased IRS- 2-associated phosphatidylinositol (PI) 3-kinase activity. The mitogenic effects of insulin, IGF-I, and IGF-II were markedly attenuated by the PI 3- kinase inhibitor LY 294002. Northern blot analysis of total RNA extracted from normal and cancerous tissues revealed that IRS-2 mRNA levels were increased in the cancer tissues (P = 0.032). In the normal pancreas, IRS-2 immunoreactivity was present at low levels in some ductal and acinar cells and at moderate levels in a heterogeneous pattern in all of the endocrine islets. In the pancreatic cancers, IRS-2 was abundant in the ductal-like cancer cells. These findings indicate that IRS-2 is overexpressed in human pancreatic cancer and suggest that it may contribute to enhanced mitogenic signaling via the PI 3-kinase pathway, thereby leading to excessive growth stimulation in this malignancy.

Original languageEnglish (US)
Pages (from-to)4250-4254
Number of pages5
JournalCancer Research
Volume58
Issue number19
StatePublished - Oct 1 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kornmann, M., Maruyama, H., Bergmann, U., Tangvoranuntakul, P., Beger, H. G., White, M. F., & Korc, M. (1998). Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer. Cancer Research, 58(19), 4250-4254.