Protease inhibitors do not block transformed cells in the G₁ phase of the cell cycle

Abstract

PROTEOLYTIC treatment releases normal fibroblasts from density-dependent inhibition of growth (DDI)^1,2 and induces surface properties characteristic of transformed cells. Furthermore, increased^3–5 and altered⁶ protease activities are found in transformed cells. Also, a number of commercially available protease inhibitors including N-α-tosyl-L-lysyl-chloromethane (TLCK) selectively inhibit the growth of transformed cells⁷. All this has led to the suggestion that a protease-like activity is required by transformed cells for unrestrained growth⁷ and, by inference, that inhibition of this activity should restore ‘normal’ growth control (that is, DDI). In fact, TLCK lowers the saturation density⁷, decreases the agglutinability with lectins and induces ‘flat’ morphology in transformed cells⁸. Here we present evidence that TLCK-inhibited cells are, however, not arrested in the G₁ phase of the cell cycle; thus, they do not meet a primary criterion⁹ for density-dependent inhibition of growth.