Transforming growth factor(s) production enables cells to grow in the absence of serum: an autocrine system.

Abstract

Kirsten murine sarcoma virus (KiMSV)-transformed rat-1, normal rat kidney (NRK) and BALB/c 3T3 cells are capable of continual growth in a serum-free medium supplemented with transferrin and insulin but with no exogenous mitogenic growth factors. Cells transformed by a mutant of KiMSV that is temperature-sensitive for the maintenance of transformation grow in this medium at the permissive temperature only. At the nonpermissive temperature, growth is dependent upon the presence of serum-free conditioned medium from the transformed cells. Normal rat-1 cells are also dependent upon factors from the transformed cells for growth in this serum-free/mitogen-free medium. The serum-derived growth factors, epidermal growth factor and fibroblast growth factor have no effect on the transformed cells, although epidermal growth factor can replace transforming growth factors produced by KiMSV-transformed cells for the growth of rat-1 cells. Growth of the transformed cells in serum-free medium at clonal densities is dependent upon the presence of conditioned medium collected from the same cells grown to high densities. Growth in serum-serum-free/mitogen-free medium is a general property of KiMSV-transformed cells, and growth of the transformed cells in this medium is dependent upon the presence of growth factors known to be produced by the cells. Serum-free growth of KiMSV-transformed cells appears to be dependent upon ectopically-produced growth factors.