The role of the insulin-like growth factor I receptor in the transformation by simian virus 40 T antigen.

Balb/c 3T3 cells transformed by the tsA58 temperature-sensitive (ts) mutant of SV40 large T antigen, BalbA58 cells, grow in 1% serum at the permissive temperature of 34 degrees C but fail to grow at the restrictive temperature of 39.6 degrees C. Although incapable of growing, BalbA58 cells, in low serum at 39.6 degrees C, still synthesize DNA and tend to accumulate in the G2 phase of the cell cycle. Growth in 1% serum at 39.6 degrees C resumes if BalbA58 cells are treated with insulin-like growth factor I (IGF-I). By using cells overexpressing the IGF-I receptor, and cells with a targeted disruption of the IGF-I receptor genes, we show that: 1) the activation of the IGP-I receptor by its ligand(s) plays a major role in the ability of the SV40 large T antigen to promote growth in low serum; and 2) the IGF-I receptor plays a role in the progression of cells not only through G1, but also through the S and G2 phases of the cell cycle. These findings, together with other recent findings from the literature, suggest that one of the mechanisms by which oncogenes and tumor suppressor genes regulate cell growth is through the modulation of growth factors and their receptors.