Cells transformed by adenovirus type 12 but not by type 5 are dependent on insulin or insulin-like growth factor I for their proliferation

We have investigated the responsiveness to growth factors (GFs) of primary baby rat kidney (BRK) cells transformed by the E1 region of adenovirus 5 or 12. The in vitro growth of non-oncogenic adenovirus 5-transformed BRK cells is largely independent of serum GFs, whereas growth of highly oncogenic adenovirus 12-transformed cells is strictly dependent on GFs present in serum. For the growth of adenovirus 12 E1-transformed BRK cells serum can be replaced by insulin or insulin-like growth factor-I but not by epidermal growth factor. To maintain the in vitro growth of adenovirus 12-transformed cells physiological levels of insulin-like growth factor-I, but not of insulin, are sufficient. Similar results have been found with adenovirus-transformed primary murine cells and with transformants of an established rat cell line, NRK 49F. This indicates that the observed GF responsiveness is not dependent of the cell type used but is determined by the serotype of the adenovirus-transforming region. Using hybrid E1 regions consisting of E1A of one serotype and E1B of the other, we show that the pattern of GF-responsiveness correlates with the origin of the E1A region. The differences in the GF-responsiveness of the adenovirus 5-transformed and adenovirus 12-transformed cells will be discussed in terms of the oncogenicity of these cells.