Effect of a phorbol ester on a transformation-sensitive surface protein of chick fibroblasts

Abstract

PMA (phorbol myristate acetate) is the most active of a class of compounds present in croton oil which act as tumour promoters^1–3. While PMA possesses little car-cinogenicity in its own night, its repeated application to mouse skin causes tumour induction in animals treated up to several months previously with a single subthreshold dose of a carcinogen. If the order of treatments is reversed, that is, if PMA treatment precedes that with the carcinogen, then no tumours are induced. Studies both with mouse skin and with cells in tissue culture indicate substantial effects of PMA on cell behaviour and biochemistry. Many of these effects such as alteration of phospholipid synthesis⁴ or stimulation of Na⁺, K⁺-ATPase and 5′-nucleotidase⁵ relate to the cell membrane. We report here that PMA alters the cell surface protein composition of chick embryo fibroblasts, causing a decrease in the major surface protein LETS (molecular weight 250,000). Previous work by several laboratories has indicated that LETS, which is present on the surface of fibroblasts from a variety of species, either decreases or disappears upon transformation^6–11. Although LETS is highly sensitive to cleavage by proteases such as plasmin¹², its mechanism of loss following transformation remains to be clarified.