Similar effects of phospholipase C and phorbol ester tumor promoters on primary mouse epidermal cells

Journal Article · Fri Nov 01 00:00:00 EST 1985 · Cancer Res.; (United States)

OSTI ID:6297669

Jeng, A Y; Lichti, U; Strickland, J E; Blumberg, P M

Interaction of tumor promoting phorbol esters with specific high affinity receptors is probably essential for many of the biological responses elicited by these agents. Since diacylglycerols which can be produced enzymatically from phospholipids by phospholipase C are postulated to be the physiological ligands for the phorbol ester receptor, the authors have examined primary cultures of mouse epidermal basal cells exposed to phospholipase C (Clostridium perfringens) for several biological and biochemical responses characteristic of treatment with 12-O-tetradecanoyl-phorbol-13-acetate, the most potent phorbol ester tumor promoter. Formation of diacylglycerols by treatment with phospholipase C was demonstrated by the dose-dependent release of radioactive diacylglycerols in cells prelabeled with (TH)arachidonic acid. Treatment with phospholipase C led to the morphological changes and to the reduction in epidermal growth factor binding (90%) associated with 12-O-tetradecanoylphorbol-13-acetate treatment. Continuous treatment at the same dose led to the induction of the enzymes ornithine decarboxylase and transglutaminase with a time course and extent similar to the inductions by 12-O-tetradecanoylphorbol-13-acetate. Treatment with phospholipase C yielded substantial suppression of the binding affinity of phorbol-12,13-dibutyrate for its receptors without reduction in total number of binding sites, consistent with the production by phospholipase C of a competitive inhibitor of phorbol ester binding.

• Research Organization: National Cancer Institute, Bethesda, MD
• OSTI ID: 6297669
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
MORPHOLOGICAL CHANGES
LIPASE
BIOLOGICAL EFFECTS
PHORBOL ESTERS
ARACHIDONIC ACID
ENZYME INDUCTION
EPIDERMIS
MICE
RECEPTORS
TRITIUM COMPOUNDS
ANIMAL TISSUES
ANIMALS
BODY
CARBOXYLESTERASES
CARBOXYLIC ACIDS
CARCINOGENS
ENZYMES
EPITHELIUM
ESTERASES
ESTERS
GENE REGULATION
HYDROLASES
LABELLED COMPOUNDS
MAMMALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RODENTS
SKIN
TISSUES
VERTEBRATES
550301* - Cytology- Tracer Techniques