βIII-Tubulin is required for interphase microtubule dynamics in untransformed human mammary epithelial cells

Abstract

Numerous works have questioned the pertinence of using βII- and/or βIII-tubulin expression as markers of prognosis and/or prediction of breast cancer response to chemotherapy containing microtubule-targeting agents. The rationale of such studies was essentially based on microtubule dynamics analysis using purified tubulin in vitro and cancer cell lines. Nonetheless, the significance of βII- and βIII-tubulin expression in the control of microtubule dynamics in normal mammary epithelium has never been addressed. Here we investigate the expression and the consequences of βII- and/or βIII-tubulin depletion in interphase microtubule dynamics in non-tumor human mammary epithelial cells. We find that both isoforms contribute to the tubulin isotype composition in primary and immortalized human mammary epithelial cells. Moreover, while βII-tubulin depletion has limited effects on interphase microtubule behavior, βIII-tubulin depletion causes a strong exclusion of microtubules from lamella and a severe suppression of dynamic instability. These results demonstrate that, while βII-tubulin is dispensable, βIII-tubulin is required for interphase microtubule dynamics in untransformed mammary epithelial cells. This strongly suggests that βIII-tubulin is an essential regulator of interphase microtubule functions in normal breast epithelium cells.