Loss of Cell Adhesion to Substratum Up-Regulates p21Cip1/WAF1Expression in BALB/c 3T3 Fibroblasts

Abstract

Cell adhesion to substratum is essential for the transition of G1 to S phase in mouse BALB/c 3T3 fibroblast cell cycle. Loss of cell adhesion in late G1 phase caused blockage of the G1/S phase transition and repression of cyclin E-associated cyclin-dependent kinase-2 (CDK2) activity. A CDK2 inhibitor abundant in quiescent cells, p27Kip1, was down-regulated by growth factors in serum, and this down-regulation was partially prevented by loss of cell adhesion. Another CDK2 inhibitor, p21Cip1/WAF1, which was undetectable in quiescent cells, was markedly induced by loss of cell adhesion. In exponentially growing cells, loss of cell adhesion also induced p21Cip1/WAF1expression but did not affect the abundance of p27Kip1. These results suggest that loss of cell adhesion to substratum up-regulates p21Cip1/WAF1expression, which plays an essential role for arresting the BALB/c 3T3 fibroblast cell cycle.