Role of calcium in prolactin-stimulated c-myc gene expression and mitogenesis in Nb2 lymphoma cells

Journal Article · Wed Jun 01 00:00:00 EDT 1988 · Endocrinology; (United States)

OSTI ID:7141033

Murphy, P R; DiMattia, G E; Friesen, H G

Receptor-activated transmembrane calcium flux has been implicated as a mediator of the actions of many growth factors and hormones. We examined the effects of PRL, calcium ionophores, and calcium antagonists on /sup 45/Ca2+ flux, c-myc gene expression, and DNA synthesis in the PRL-dependent rat Nb2 lymphoma cell line. PRL had no detectable effects on /sup 45/Ca2+ uptake or efflux, and the mitogenic effects of PRL could not be reproduced by the calcium ionophore A23187 alone or in combination with the tumor-promoting phorbol ester 12-O-tetra-decanoyl-phorbol-13 acetate (TPA). PRL, but not A23187 or TPA, stimulated c-myc gene expression in quiescent Nb2 cells. Exposure to PRL for brief periods (15 min to 4 h), followed by extensive washing, resulted in a time- and dose-dependent activation of DNA synthesis measured 16 h later. This activation was not blocked by addition of excess anti-PRL antiserum after the wash steps, indicating that the observed stimulation was not due to residual PRL. Despite the marked increase in DNA synthesis, removal of PRL after 4 h prevented mitosis, suggesting that PRL may be required throughout the cell cycle for Nb2 cell proliferation. Although continuous incubation with calcium antagonists resulted in a dose-dependent inhibition of PRL-stimulated DNA synthesis, activation of DNA synthesis by brief exposure to PRL was not inhibited by the presence of EGTA, calcium channel blockers (nifedipine, cobalt chloride), or calmodulin inhibitors (trifluoperazine, N-6-aminohexyl-5-chloronaphthalene sulfonamide). PRL-stimulated c-myc expression was attenuated, but not blocked, by the calcium channel antagonists. However, the putative intracellular calcium antagonist TMB-8 inhibited both c-myc expression and DNA synthesis in a dose-dependent manner (IC50 = 16 microM).

• Research Organization: Univ. of Manitoba, Winnipeg (Canada)
• OSTI ID: 7141033
• Journal Information: Endocrinology; (United States), Vol. 122:6
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CALCIUM
BIOLOGICAL FUNCTIONS
MEMBRANE TRANSPORT
PHORBOL ESTERS
CARCINOGENESIS
TUMOR CELLS
GENE REGULATION
CALCIUM 45
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
EGTA
GALLIC ACID
LTH
MITOGENS
RATS
TRACER TECHNIQUES
ALCOHOLS
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METALS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CALCIUM ISOTOPES
CARBOXYLIC ACIDS
CARCINOGENS
CHELATING AGENTS
DAYS LIVING RADIOISOTOPES
ELEMENTS
ESTERS
EVEN-ODD NUCLEI
FUNCTIONS
GLYCOLS
GONADOTROPINS
HORMONES
HYDROXY ACIDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
METALS
NUCLEI
NUCLEIC ACID REPLICATION
ORGANIC ACIDS
ORGANIC COMPOUNDS
PATHOGENESIS
PEPTIDE HORMONES
PITUITARY HORMONES
RADIOISOTOPES
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques
560300 - Chemicals Metabolism & Toxicology