Cell cycle arrest in G0/G1 phase by contact inhibition and TGF-beta 1 in mink Mv1Lu lung epithelial cells.
We postulated that contact inhibition and transforming growth factor (TGF)-beta 1 may target the same molecules to negatively regulate the Mv1Lu cell cycle in G0/G1. Both contact inhibition and TGF-beta 1 suppressed the expression of a 45-kDa protein (p45); cyclins D2 and B1; cyclin-dependent protein kinase (Cdk)-4, Cdc-2, and Cdc-2-associated activity; and the phosphorylation of retinoblastoma tumor-suppressor protein (pRb) but did not affect the expression of cyclins D1, E, and A or the expression of Cdk-2 and Cdk-5. Expression of p45 reappeared 12 h after release from contact inhibition and 6-8 h after release from TGF-beta 1, while TGF-beta 1 prevented release from contact inhibition and maintained suppression of both p45 and cyclin D2. Additionally, cyclin D2 phosphorylation and its associated kinase activity were strongly inhibited by contact inhibition and TGF-beta 1. Thus suppression of p45, cyclin D2/Cdk-4, and cyclin B1/Cdc-2 expression and/or activities is targeted both by contact inhibition and by TGF-beta 1 and may define common mechanisms through which these negative growth signals are integrated.
Wu
F
F
Department of Surgery, Children's Hospital of Los Angeles, California, USA.
Buckley
S
S
Bui
K C
KC
Yee
A
A
Wu
H Y
HY
Liu
J
J
Warburton
D
D
D000818:Animals; D002450:Cell Communication; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D056742:Cyclin D2; D016213:Cyclins / Q000378:metabolism; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D016193:G1 Phase; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000166:cytology* / Q000187:drug effects*; D008907:Mink / Q000196:embryology; D010766:Phosphorylation / Q000187:drug effects; D016192:Resting Phase, Cell Cycle; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D016212:Transforming Growth Factor beta