We present data that extend the present models of transformation and tumor cell progression by one essential step. In vitro, cocultivation of transformed and normal fibroblasts in the presence of TGF-beta leads to the specific elimination of transformed cells due to induction of apoptosis. This mechanism may represent an effective control step early in carcinogenesis. We propose that in vivo, this control mechanism eliminates arising transformed cells unless certain chemicals interfere with this process or the transformed cells have acquired resistance against it. Acquisition of resistance may be an essential requirement for tumor progression.

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