Cell transformation mutants are not susceptible to growth activation by fibroblast growth factor at permissive temperatures

Abstract

CHEMICAL¹ or viral² transformation of fibroblasts in tissue culture results in cell variants with different properties from the original cells (see ref. 2 for review). These properties include morphological changes, surface alterations³ and an increased growth ability under various conditions. This changed pattern in growth control of many transformed cells is manifested in vitro by their ability to grow in agar, to attain higher saturation densities in monolayer cultures and to be much less responsive to inhibition of cell multiplication by serum limitation^4,5. In addition, different fractions of serum stimulate the growth of untransformed mouse 3T3 fibroblasts and 3T3 cells transformed by SV40 (SV3T3) in culture⁶ which suggests the involvement of different growth promoting molecules for normal and transformed cells. It has been shown that a new pituitary hormone, fibroblast growth factor⁷ (FGF), with a glucocorticoid, hydrocortisone, and with a nonspecific carrier protein could completely replace exogenously added serum for the induction of the complete mitogenic response in lines of BALB/c 3T3 cells⁷, whereas virtually no effects were observed on virally transformed cells (P. S. R., W. S. and D. G.; manuscript in preparation). In the presence of serum exhausted for its growth-initiating ability only FGF was required to initiate or increase DNA synthesis and cell division; the hydrocortisone concentration present in serum was considered to be sufficiently high not to require further addition⁷. We have now investigated the ability of FGF to promote the growth of cell mutants of BALB/c 3T3 which show temperature dependent changes in many properties characteristic of the transformed state (W. E., manuscript in preparation). We found that FGF initiates DNA synthesis and cell multiplication only at the non-permissive temperatures (‘normal’ state) but fails to initiate or promote cell growth at permissive temperatures (transformed state).