Rapid induction of competence formation is PDGF‐isoform specific

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Abstract
Platelet‐derived growth factor (PDGF) stimulates the expression of a number of genes associated with entry of quiescent Balb/c‐3T3 fibroblasts into the cell cycle. We determined that two of these genes, c‐myc and c‐fos, are induced equivalently in medium supplemented with platelet‐poor plasma (PPP) and either PDGF‐BB or PDGF‐AA. The rate at which fibroblasts entered S phase was also similar in PDGF‐BB– and AA–treated cells as was the expression of the late G1 gene, thymidine kinase (TK). However, PDGF‐AA must be present for a period of 16 h to stimulate the proliferation of 90% of the cells, whereas PDGF‐BB was required for only 4 h. Exposure of cells to PDGF‐AA for 4 h, a time during which maximum expression of c‐fos and c‐myc occurred, only induced 20% of the cells in a quiescent population to enter the cell cycle. Therefore, PDGF‐AA–mediated expression of the immediate early genes c‐fos and c‐myc may be necessary but is not sufficient to rapidly stimulate density‐arrested Balb/c‐3T3 fibroblasts into the competent state. Thus, these data suggest that PDGF‐AA and PDGF‐BB initiate traverse of the cell cycle by distinct mechanisms.