Induction of expression of c-fos and c-myc protooncogenes by basic calcium phosphate crystal: effect of beta-interferon.
Basic calcium phosphate (BCP) crystals control the traverse of cells from the G0-G1 to S-phase of the cell cycle and initiate proliferation by rendering fibroblasts competent to respond to insulin-like growth factors in plasma. The present study examines whether BCP crystals induce transcription of the protooncogenes c-fos and c-myc and the effect of beta-interferon (IFN-beta) on protooncogene transcription as well as BCP crystal-induced DNA synthesis. Stimulation of density-arrested BALB/c-3T3 cells with either BCP crystal or platelet-derived growth factor (PDGF) results in maximal accumulation of c-fos mRNA at 30 min after stimulation. Induction of c-myc transcription by BCP crystal or PDGF occurs within 1 h and is maximal at around 3 h after stimulation. Simultaneous addition of IFN-beta with either BCP crystals or PDGF had little effect on c-fos induction but delayed both c-myc message accumulation and entry into S phase. The delay in c-myc message induction after IFN-beta treatment cannot account for the observed delay in the onset of DNA synthesis, since IFN-beta can be added at up to 6 h after stimulation with either PDGF or BCP crystals, and a similar delay in the onset of DNA synthesis is still observed.
Cheung
H S
HS
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Mitchell
P G
PG
Pledger
W J
WJ
D002130:Calcium Phosphates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003460:Crystallization; D004247:DNA / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011519:Proto-Oncogenes
D002130:Calcium Phosphates; D010982:Platelet-Derived Growth Factor; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; D007371:Interferon-gamma; D004247:DNA; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous