INHIBITION OF ABELSON ONCOGENE FUNCTION BY ERBSTATIN ANALOGS

The authors examined the effect of a tyrosine kinase inhibitor, erbsta tin, and its analogues on abl oncogene functions. Erbstatin and its st able analogue methyl 2,5-dihydroxycinnamate (2,5-MeC) inhibited the gr owth of v-abl(ts)-NIH3T3 cells at the permissive temperature (33 degre es C) at lower concentrations than at the non-permissive temperature ( 39 degrees C). 2,5-MeC inhibited the morphological transformation and the activation of v-abi tyrosine kinase by the temperature shift (39 d egrees C to 33 degrees C) more effectively than erbstatin. Previously the authors reported that erbstatin induced erythroid differentiation of K562 human chronic myelogenous leukaemia cells, so they examined th e effect of erbstatin analogues on the erythroid differentiation. Amon g eight erbstatin analogues studied, ethyl 2,5-dihydroxycinnamate indu ced erythroid differentiation of K562 cells most effectively. Ethyl 2, 5-dihydroxycinnamate also inhibited bcr-abi tyrosine kinase. These res ults indicate that the stable analogues of erbstatin suppress oncogene functions of Abl by inhibiting its tyrosine kinase.