TAU EXPRESSION IN MODEL ADENOCARCINOMAS CORRELATES WITH DOCETAXEL SENSITIVITY IN TUMOR-BEARING MICE

Docetaxel is a new taxoid with clinical activity in breast and lung ca ncer. Using docetaxel-sensitive and -refractory mammary and pancreatic murine tumours, as well as human-derived neoplasms, we investigated i f a determinant of docetaxel sensitivity could be found at the level o f its mechanism of action. Because microtubules represent the cellular targets of the drug, we studied their heterogeneity in the tumour mod els to try to explain the differences in drug sensitivity Reverse tran scription-polymerase chain reaction (RT-PCR) analysis of the expressio n of microtubular components showed that levels of M beta 4-tubulin an d Tau mRNAs were higher in the murine sensitive neoplasms than in the refractory ones, It was also found that Tau protein levels differed ma rkedly among the tumours. In the human-derived sensitive neoplasm, bet a-tubulins and some Tau isoforms were found to be more abundant than i n the resistant one. Western blot analysis of MAP2 revealed the presen ce of several immunoreactive species. Some of these polypeptides were also found in higher amounts in the docetaxel-sensitive tumours. The p ossible meaning of these correlations is discussed in connection with the regulation of microtubule dynamics.