Involvement of Cell Cycle and Mitogen-Activated Pathways in Induction of Parathyroid Hormone-Related Protein Gene Expression in Rat Aortic Smooth Muscle Cells*

PTH-related protein (PTHrP) is induced in aortic vascular smooth muscle cells (VSMC) in association with mitogen-stimulated proliferation. In this study we examined the role of the cell cycle in the control of PTHrP gene expression. In asynchronously cycling cells grown in serum-containing medium, PTHrP-immunoreactive cells were enriched in G2+M, as revealed by fluorescence-activated cell sorting using a specific monoclonal antibody. PTHrP messenger RNA (mRNA) increased transiently in cells after release from chemically induced cell cycle blockade; levels increased by 10-fold at 2 h, coincident with expression of histone-4 mRNA and enrichment of VSMC in the early S phase. However, PTHrP mRNA levels then declined abruptly while the proportion of cells in the S phase and histone-4 mRNA levels remained constant for 8 h. When cell cycle-arrested cells were exposed to fresh serum-containing medium, angiotensin-II, or phorbol ester without removing the cell cycle blocking agents, PTHrP mRNA levels were induced ...