Control of c-fos and c-myc proto-oncogene induction in rat thyroid cells in culture

Journal Article · Sun Nov 01 00:00:00 EST 1987 · Molecular Endocrinology; (USA)

DOI:https://doi.org/10.1210/mend-1-11-839· OSTI ID:6318200

Isozaki, O; Kohn, L D ^[1]

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1. National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD (USA)

Removal of TSH, insulin, and cortisol from the medium, and decreasing the serum content to 0.2%, abolishes both the proliferate and differentiated state of FRTL-5 rat thyroid cells in culture. In these basal conditions, the individual addition of TSH, insulin, insulin-like growth factor-I (IGF-I), phorbol 12-myristate 13-acetate (TPA), alpha 1-adrenergic agents, or A23187, increase c-myc and/or c-fos proto-oncogene expression. Under the same conditions, only the addition of TSH increased cAMP levels; 8-bromo-cAMP can increase c-myc or c-fos mRNA levels. Pretreatment of cells with phorbol 12,13-dibutyrate, an agent which down regulates the C-kinase, completely inhibits the effect of TPA on proto-oncogene expression but has no affect on the A23187 induced-increase. The sum of these results indicate that at least four separate signal systems independently increase c-myc or c-fos gene expression in FRTL-5 cells cAMP (TSH), C-kinase (TPA), Ca++/phosphoinositide (A23187), and that influenced by insulin/IGF-I. None of the ligands, when individually returned to cells in basal medium (no TSH, insulin, or cortisol and only 0.2% serum), increases cell number; norepinephrine, and A23187 do not increase (3H)thymidine incorporation into DNA under these conditions; and combinations of the ligands can be more than additive in effecting (3H)thymidine incorporation into DNA but are only additive in effecting proto-oncogene expression. Insulin/IGF-I plus TSH or insulin/IGF-I plus norepinephrine can increase both proto-oncogene expression and (3H)thymidine incorporation into DNA to the same extent; however, the former combination can increase cell number whereas the latter cannot. There is therefore no simple correlation between the ability of the above ligands to increase proto-oncogene expression and their ability to increase cell number or induce DNA synthesis.

• OSTI ID: 6318200
• Journal Information: Molecular Endocrinology; (USA), Vol. 1:11; ISSN 0888-8809
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
GROWTH FACTORS
BIOLOGICAL EFFECTS
INSULIN
PHORBOL ESTERS
THYROID CELLS
GENE REGULATION
TSH
CELL PROLIFERATION
DNA
LIGANDS
MESSENGER-RNA
NORADRENALINE
ONCOGENES
RATS
THYMIDINE
THYROGLOBULIN
THYROID
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADRENAL HORMONES
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BODY
CARCINOGENS
CARDIOTONICS
CARDIOVASCULAR AGENTS
DRUGS
ENDOCRINE GLANDS
ESTERS
GENES
GLANDS
GLOBULINS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MAMMALS
MITOGENS
NEUROREGULATORS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
PYRIMIDINES
RIBOSIDES
RNA
RODENTS
SYMPATHOMIMETICS
VERTEBRATES
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