DIFFERENCES IN THE MECHANISMS OF GROWTH-CONTROL IN CONTACT-INHIBITED AND SERUM-DEPRIVED HUMAN FIBROBLASTS

In the present work we studied mechanisms of growth control in contact -inhibited and serum-deprived human diploid fibroblasts. The observati on that the effects on [H-3]thymidine incorporation and reduction of r etinoblastoma gene product-phosphorylation were additive when contact- inhibition and serum-deprivation were combined led us to the conclusio n that the underlying mechanisms might be different. Both contact-inhi bition and serum-deprivation led to a strong decrease of cdk4-kinase-a ctivity and cdk2-phosphorylation at Thr 160, while the total amounts o f cdk4 and cdk2 remained constant. In contact-inhibited cells, we reve aled a strong protein accumulation of the cdk2-inhibitor p27 and a sli ght, but significant increase of the cdk4-inhibitor p16. In serum-depr ived cells, the protein levels in p27 and p16 remained low. In contras t, we detected a rapid decrease of cyclin D1 and cyclin D3 which did n ot occur in contact-inhibited cells. These results indicate that serum -deprivation and contact-inhibition have different mechanisms although they affect the same pathway cyclin D-cdk4, pRB, cyclin E-cdk2.