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Induction of Expressions of c-fos and c-myc Protooncogenes by Basic Calcium Phosphate Crystal: Effect of ß-Interferon¹

Division of Rheumatology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 [H. S. C.], and Department of Cell Biology, Vanderbilt University, School of Medicine, Nashville, Tennessee 37232 [P. G. M., W. J. P.]

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 ß-interferon (IFN-ß) 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-ß 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-ß treatment cannot account for the observed delay in the onset of DNA synthesis, since IFN-ß 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.

¹ This work was supported in part by USPHS Grants AR38421 (H. S. C.), CA42713 (W. J. P.), and CA42636 (W. J. P.) and by Research Career Development Award AM 1065 (H. S. C.).

² Present address: Division of Rheumatology, Department of Medicine, Medical College of Wisconsin, 8700 W. Wisconsin Ave., Milwaukee, WI 53226.

Received 7/ 6/88. Revised 9/29/88. Accepted 10/ 4/88.

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