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) m utant 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 restric tive temperature of 39.6 degrees C. Although incapable of growing, Bal bA58 cells, in low serum at 39.6 degrees C, stilt synthesize DNA and t end to accumulate in the G(2) phase of the cell cycle. Growth in 1% se rum at 39.6 degrees C resumes if BalbA58 cells are treated with insuli n-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 l igand(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 rol e in the progression of cells not only through G(1), but also through the S and G(2) phases of the cell cycle. These findings, together with other recent findings from the literature, suggest that one of the me chanisms by which oncogenes and tumor suppresser genes regulate cell g rowth is through the modulation of growth factors and their receptors.