HYPERPHOSPHORYLATION OF RETINOBLASTOMA PROTEIN AND STIMULATION OF GROWTH BY OKADAIC ACID IN HUMAN PANCREATIC-CANCER

Phosphorylation/dephosphorylation of intracellular proteins are import ant steps in the regulation of cell growth. Okadaic acid, an inhibitor of the serine/threonine protein phosphatases 1 and 2A, is a potent tu mor promoter. This effect may be through the inhibition of dephosphory lation (termed ''hyperphosphorylation'') and subsequent inactivation o f tumor-suppressor proteins. We examined whether okadaic acid regulate s growth of human pancreatic cancer cells (MIA PaCa-2 and Panc-1) or a lters the phosphorylation of the retinoblastoma tumor-suppressor prote in. Growth studies, nuclear labeling analyses, and Western blotting fo r 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 pancreat ic cancer cells may be mediated by inactivation of the growth suppress ive effect of the retinoblastoma protein by hyperphosphorylation. Thes e studies suggest that the growth of these human pancreatic cancer cel ls is still regulated by tumor-suppressor proteins.