Phorbol ester inhibition of an insulin-stimulated growth response
Insulin was previously shown to stimulate a growth response in quiescent Reuber H-35 rat hepatoma cells in culture. This effect was demonstrated to be mediated by interaction of insulin with the insulin receptor. The insulin receptor has also been demonstrated to be phosphorylated in response to the tumor promoter, tetradecanoyl phorbol acetate (TPA). This phosphorylation of the receptor was postulated to render the cells refractory to the effects of insulin. TPA inhibits the growth stimulatory effects of insulin with half-maximal inhibition occurring at approximately 10nM TPA. Phorbol dibutyrate is less potent than TPA and phorbol diacetate and 4-B-phorbol are essentially inactive. In experiments designed to determine the time most sensitive to the inhibitory effects of TPA, it was found that if TPA is added within the first four hours following the addition of insulin, inhibition is still maximal. The effect of TPA can be completely reversed if it is added simultaneously with insulin but washed out at two or four hours. These results suggested that the cellular events which mediate the inhibitory effects of the phorbol esters occur at least three to four hours following the addition of insulin. Kinetic experiments demonstrated that TPA did not alter the minimal lag period prior to the entry into S phase but appears to inhibit that rate of entry into S phase.
- Research Organization:
- Univ. of Tennessee, Knoxville
- OSTI ID:
- 6840097
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
INSULIN
RECEPTORS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHORYLATION
TUMOR CELLS
GROWTH
BIOCHEMICAL REACTION KINETICS
INHIBITION
ANIMAL CELLS
CARCINOGENS
CHEMICAL REACTIONS
ESTERS
HORMONES
KINETICS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PROTEINS
REACTION KINETICS
560300* - Chemicals Metabolism & Toxicology
550900 - Pathology