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

68 Citations (Scopus)

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
Externally publishedYes

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Insulin Receptor Substrate Proteins
Pancreatic Neoplasms
Phosphatidylinositol 3-Kinase
Insulin-Like Growth Factor II
Insulin
Insulin-Like Growth Factor I
Cell Line
Neoplasms
IGF Type 1 Receptor
Messenger RNA
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Acinar Cells
Growth
Northern Blotting
Tyrosine
Pancreas
Proteins
Phosphorylation
RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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.

Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer. / Kornmann, Marko; Maruyama, Haruhisa; Bergmann, Uwe; Tangvoranuntakul, Pam; Beger, Hans G.; White, Morris F.; Korc, Murray.

In: Cancer Research, Vol. 58, No. 19, 01.10.1998, p. 4250-4254.

Research output: Contribution to journalArticle

Kornmann, M, Maruyama, H, Bergmann, U, Tangvoranuntakul, P, Beger, HG, White, MF & Korc, M 1998, 'Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer', Cancer Research, vol. 58, no. 19, pp. 4250-4254.
Kornmann M, Maruyama H, Bergmann U, Tangvoranuntakul P, Beger HG, White MF et al. Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer. Cancer Research. 1998 Oct 1;58(19):4250-4254.
Kornmann, Marko ; Maruyama, Haruhisa ; Bergmann, Uwe ; Tangvoranuntakul, Pam ; Beger, Hans G. ; White, Morris F. ; Korc, Murray. / Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer. In: Cancer Research. 1998 ; Vol. 58, No. 19. pp. 4250-4254.
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