New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues.

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Abstract
Proteins potentiated by epidermal growth factor (EGF) to induce a transformed phenotype in non-neoplastic rat kidney fibroblasts in cell culture were isolated from many non-neoplastic tissues of the adult mouse, including submaxillary gland, kidney, liver, muscle, heart and brain. They resemble previously described transforming growth factors (TGF) isolated from neoplastic cells as follows: they are extractable by acid/ethanol and are acid-stable, low MW (6000-10,000) polypeptides requiring disulfide bonds for activity and they cause anchorage-independent growth of non-neoplastic indicator cells that will not grow in soft agar in their absence. Partial purification of these TGF from submaxillary glands of male mice shows that they are distinct from EGF. Unlike previously described extracellular TGF, but like certain cellular TGF from neoplastic cells, they are potentiated by EGF in their ability to promote anchorage-independent growth. The isoelectric point of the submaxillary gland TGF protein is near neutrality. Chromatography on Bio-Gel P-30 followed by high-pressure liquid chromatography has resulted in a 22,000-fold overall purification. The most purified protein is active in inducing growth in soft agar at 1 ng/ml when assayed in the presence of EGF. Neoplasia may result from a quantitative, rather than qualitative, alteration in non-neoplastic biochemical processes.