Platelet-derived growth factor prevents G₀ growth arrest

Abstract

Baserga¹ has summarised evidence that there are two growth states in which cells have a diploid content of DNA; G₁—the interval between mitosis and S phase in exponentially growing cultures—and G₀, a quiescent state entered only when conditions for growth are suboptimal. G₀ can be distinguished from G₁ by temporal measurements; for BALB/c 3T3 cells, the lag time between G₀ and S phase is never shorter than 12 h (ref. 2), whereas in exponentially growing cells the mean lag time between mitosis and S (G₁ by definition) lasts 5–6 h (ref. 3). G₀ can also be distinguished from G₁ by some biochemical parameters including G₀- and G₁-specific intracellular proteins^4,5. SV40- or polyoma virus-transformed cells cannot enter G₀ to become quiescent^6–9. Serum induces the growth of BALB/c 3T3 cells in tissue culture. It sustains the growth of exponentially replicating populations, and causes density-inhibited cells to leave G₀ and replicate^10–12. Serum contains several sets of hormonal growth factors which have recently been defined^2,13,14. One of these hormones, the platelet-derived growth factor (PDGF), is released into serum during the clotting process; PDGF is absent in platelet-poor plasma, the liquid portion of unclotted blood^15–19. It promotes the growth of G₀-arrested cells^2,16 by stimulating cells to become ‘competent’ to enter the S phase²; plasma allows these competent cells to progress through G₀/G₁, synthesise DNA^2,20 and divide¹³. We now show that PDGF has a second function. It prevents replicating cells from entering G₀.