Differentiation of human colon cancer cells changes the expression of beta-tubulin isotypes and MAPs

The human colon adenocarcinoma HT29-D4 cell line is an interesting model fo r studies an epithelial cell differentiation. Undifferentiated cells are ma lignant proliferating cells, whereas differentiated cells act like epitheli al polarized cells. In the present study, we first characterized the action of taxoids on the microtubular network of HT29-D4 cells according to the s tate of differentiation. Microtubular bundles were found in undifferentiate d cells but not in differentiated cells, even with 500-fold higher taxoid c oncentrations for 96 h. This finding led us to study changes in microtubule s according to the polarity status of the cell. E-MAP-115 was expressed onl y in differentiated cells; expression of beta-tubulin isotypes was altered in them relative to undifferentiated cells. Classes I, II, III, IVa and IVb isotypes were expressed in both phenotypes; however, differentiated epithe lial cells displayed a specific increase in class III beta-tubulin. Thus, t he increase in expression of this beta-tubulin isotype in differentiated ce lls is not restricted to neuronal cells. Moreover, these expression changes may reflect a higher stability of microtubular network in differentiated c ells, which may explain the lower activity of anti-microtubule agents, inde pendently of the mitotic process. These results indicate that the compositi on of microtubules should be considered as one of the criteria involved in the response of tumour cells to chemotherapy with anti-microtubule agents.