The role of MAP4 expression in the sensitivity to paclitaxel and resistance to vinca alkaloids in p53 mutant cells

摘要: Mutations in p53 change the sensitivity to cancer chemotherapeutic drugs. Whereas many drugs, including vinca alkaloids, often become less effective when is transcriptionally inactivated, several, most notably paclitaxel, may more effective. In studying underlying mechanism(s), we found that increased MAP4 expression, which occurs with silent p53, associated paclitaxel and decreased alkaloids. Using murine fibroblasts transfected MAP4, directly demonstrated changes drug were parallel alterations drug-induced apoptosis cell-cycle arrest. Immunofluorescent staining of microtubule network revealed cells expression displayed an increase polymerized microtubules binding fluorsceinated paclitaxel. Since stabilizes microtubules, overexpression this gene provides a plausible mechanism explain altered microtubule-active drugs presence mutant p53.