Cyclic AMP restores a normal phenotype to sis oncogene transformed cells and inhibits inositol phospholipid turnover

Conference · Fri May 01 00:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6360613

Murphy, S K; Lazarus, A; Pendergas, M; Lockwood, A H

The sis oncogene encodes the A chain of platelet-derived growth factor (PDGF). NIH3T3 fibroblasts transfected with the cloned sis oncogene display a malignant phenotype and have enhanced turnover of the regulatory phospholipid phosphatidylinositol 4,5 biphosphate (PIP2). They have found that elevation of intracellular cyclic AMP can restore many aspects of normal growth and morphology to sis-transformed cells. Cells rapidly become less refractile, flatten on the substratum, develop actomyosin bundles, and acquire a more tranquil membrane. Growth rate and saturation density are reduced. Cultures become contact-inhibited and, at confluence, assume a normal fibrobastic morphology. The ability to grow in low serum or suspension is lost. Following addition of 8-Br-cAMP, cellular levels of PIP and PIP2 increase to those in untransformed cells. Concurrently, the steady-state levels of inositol phosphates are reduced to normal values. They have found a similar effect of cAMP on inositol phospholipid metabolism in cells transformed by the human H-ras oncogene. These results suggest that cAMP, acting through the cAMP-dependent protein kinase, antagonizes ras and sis oncogene expression by inhibiting polyphosphoinositide turnover. Such action might occur by phosphorylation of the PDGF (sis) receptor or of a ras-stimulated phospholipase C.

• Research Organization: Philadelphia College of Pharmacy and Science, PA
• OSTI ID: 6360613
• Report Number(s): CONF-870644-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 46:6; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AMP
ANIMAL CELLS
BIOLOGICAL FUNCTIONS
CONNECTIVE TISSUE CELLS
ENZYMES
ESTERS
FIBROBLASTS
FUNCTIONS
GENES
HORMONES
INHIBITION
LIPIDS
METABOLISM
MORPHOLOGY
NUCLEOTIDES
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PEPTIDE HORMONES
PHENOTYPE
PHOSPHOLIPIDS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
SOMATIC CELLS
TRANSFERASES