Abstract
Insulin-like growth factors are potent mitogenic agents for many cell types. However, IGF-I inhibits DNA synthesis and cell proliferation in lung adenocarcinoma cell line A549. IGF-I-induced inhibition was reversed by an IGF-I receptor antibody, αIR-3, indicating IGF-I receptor activation is involved in its inhibition. PD98059 (p44/42 MAPKK inhibitor) and LY294002 (PI3′-kinase inhibitor) partially reversed IGF-I-induced inhibition. Acute (2-60 min) and chronic (24h) exposure of A549 cells to IGF-I resulted in sustained phosphorylation of Akt, whereas p44/42 MAPK phosphorylation was decreased in response to chronic exposure to IGF-I. An IGF-I dose-dependent increase in the cyclin dependent kinase inhibitor p21Cip1/WAF1was also observed over 24 h treatment. These data suggest that IGF-I is growth inhibitory to A549 cells, possibly via sustained activation of the PI3′-kinase pathway, and induction of p21Cip1/WAF1
