MOLECULAR-CLONING OF A DIVERGED HOMEOBOX GENE THAT IS RAPIDLY DOWN-REGULATED DURING THE G(0) G(1) TRANSITION IN VASCULAR SMOOTH-MUSCLE CELLS/

Adult vascular smooth muscle cells dedifferentiate and reenter the cel l cycle in response to growth factor stimulation. Here we describe the molecular cloning from vascular smooth muscle, the structure, and the chromosomal location of a diverged homeobox gene, Gax, whose expressi on is largely confined to the cardiovascular tissues of the adult. In quiescent adult rat vascular smooth muscle cells, Gax mRNA levels are down-regulated as much as 15-fold within 2 h when these cells are indu ced to proliferate with platelet-derived growth factor (PDGF) or serum growth factors. This reduction in Gax mRNA is transient, with levels beginning to rise between 8 and 24 h after mitogen stimulation and ret urning to near normal by 24 to 48 h. The Gax down-regulation is dose d ependent and can be correlated with the mitogen's ability to stimulate DNA synthesis. PDGF-AA, a weak mitogen for rat vascular smooth muscle cells, did not affect Gax transcript levels, while PDGF-AB and -BB, p otent mitogens for these cells, were nearly as effective as fetal bovi ne serum. The removal of serum from growing cells induced Gax expressi on fivefold within 24 h. These data suggest that Gax is likely to have a regulatory function in the G0-to-G1 transition of the cell cycle in vascular smooth muscle cells.