6533b855fe1ef96bd12afd65

RESEARCH PRODUCT

Differences in the mechanisms of growth control in contact-inhibited and serum-deprived human fibroblasts

R.j. WieserCornelia DietrichKatja WallenfangFranz Oesch

subject

Cancer ResearchCell Cycle ProteinsProtein Serine-Threonine KinasesRetinoblastoma ProteinCulture Media Serum-FreeS PhaseCyclin D1CyclinsProto-Oncogene ProteinsCDC2-CDC28 KinasesGeneticsmedicineHumansCyclin D1Cyclin D3PhosphorylationCyclin D3FibroblastMolecular BiologyCyclin-Dependent Kinase Inhibitor p16CyclinbiologyCell growthTumor Suppressor ProteinsCyclin-Dependent Kinase 2Cyclin-dependent kinase 2G1 PhaseCyclin-Dependent Kinase 4FibroblastsDiploidyCyclin-Dependent KinasesCulture MediaCell biologymedicine.anatomical_structureCell culturebiology.proteinbiological phenomena cell phenomena and immunitySignal transductionMicrotubule-Associated ProteinsCell DivisionCyclin-Dependent Kinase Inhibitor p27

description

In the present work we studied mechanisms of growth control in contact-inhibited and serum-deprived human diploid fibroblasts. The observation that the effects on [3H]thymidine incorporation and reduction of retinoblastoma gene product-phosphorylation were additive when contact-inhibition and serum-deprivation were combined led us to the conclusion that the underlying mechanisms might be different. Both contact-inhibition and serum-deprivation led to a strong decrease of cdk4-kinase-activity and cdk2-phosphorylation at Thr 160, while the total amounts of cdk4 and cdk2 remained constant. In contact-inhibited cells, we revealed a strong protein accumulation of the cdk2-inhibitor p27 and a slight, but significant increase of the cdk4-inhibitor p16. In serum-deprived cells, the protein levels in p27 and p16 remained low. In contrast, we detected a rapid decrease of cyclin D1 and cyclin D3 which did not 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.

yearjournalcountryeditionlanguage
1997-11-27Oncogene
https://doi.org/10.1038/sj.onc.1201439