Hyperphosphorylation of retinoblastoma protein and stimulation of growth by okadaic acid in human pancreatic cancer

Aki Hirai, Richard J. Bold, Jin Ishizuka, Masashi Hirai, Courtney M. Townsend, James C. Thompson

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Phosphorylation/dephosphorylation of intracellular proteins are important steps in the regulation of cell growth. Okadaic acid, an inhibitor of the serine/threonine protein phosphatases 1 and 2A, is a potent tumor promoter. This effect may be through the inhibition of dephosphorylation (termed 'hyperphosphorylation') and subsequent inactivation of tumor-suppressor proteins. We examined whether okadaic acid regulates growth of human pancreatic cancer cells (MIA PaCa-2 and Panc-1) or alters the phosphorylation of the retinoblastoma tumor-suppressor protein. Growth studies, nuclear labeling analyses, and Western blotting for retinoblastoma protein were performed. Okadaic acid stimulated cell growth and induced hyperphosphorylation of the retinoblastoma protein. The growth-stimulatory effect of okadaic acid on these human pancreatic cancer cells may be mediated by inactivation of the growth suppressive effect of the retinoblastoma protein by hyperphosphorylation. These studies suggest that the growth of these human pancreatic cancer cells is still regulated by tumor-suppressor proteins.

Original languageEnglish (US)
Pages (from-to)1975-1980
Number of pages6
JournalDigestive Diseases and Sciences
Volume41
Issue number10
DOIs
StatePublished - Nov 13 1996

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Keywords

  • Okadaic acid
  • Pancreatic cancer
  • Retinoblastoma protein

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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