CLONAL ANALYSIS OF THE EFFECT OF TGF-BETA ON THE APOPTOSIS-INDUCING ACTIVITY OF NORMAL-CELLS

We have recently described induction of apoptosis in transformed fibro blasts by transforming growth factor type beta (TGP-beta)-treated norm al fibroblasts, which leads to the specific elimination of transformed cells. Here we investigate whether the ability to eliminate transform ed cells is the property of a specialized subpopulation of normal fibr oblasts or whether all cells within the population are able to respond to exogenous TGF-beta by induction of elimination of transformed cell s. Clonal analysis of the eliminative capacity of normal fibroblasts s howed that all cells are able to induce elimination after addition of optimal concentrations of exogenous TGF-beta. In the absence of exogen ously added TGF-beta, a minority of clones exhibited complete eliminat ive activity. Neither the ability nor the inability to perform elimina tion in the absence of exogenous TGF-beta was a stable characteristic of the respective cell clones. The number of cell clones with the abil ity to respond to suboptimal concentrations of TGF-beta increased with the passage number of the normal cells, whereas the number of clones inducing apoptosis in the absence of exogenous TGF-beta remained const ant. (C) 1995 Academic Press, Inc.