Colchicine Inhibits Epidermal Growth Factor Degradation in 3T3 Cells

Colchicine (2 μ M) did not affect the initial rate of association of125I-labeled epidermal growth factor (125I-EGF) to Swiss 3T3 cells but continued incubation (up to 24 hr) led to an increase in cell-associated radioactivity. The effect is also produced by Colcemid, vinblastine, and podophyllotoxin but not by lumicolchicine. Disruption of microtubules with colchicine does not alter the rate of ``down regulation'' of EGF receptors, suggesting that binding and internalization of the factor proceed unchanged. However, colchicine markedly decreases the rate of appearance of acid-soluble radioactivity from cells either incubated continuously with125I-EGF for 24 hr or exposed to the radioactive peptide for only 1 or 3 hr. The results indicate that colchicine decreases the rate of degradation of internalized125I-EGF. Because antitubulin agents enhance the mitogenic effect of EGF, our results suggest that peptide degradation can be dissociated from the long-term biological effect.