Cloning and sequencing of human βIII-tubulin cDNA: induction of βIII isotype in human prostate carcinoma cells by acute exposure to antimicrotubule agents

Abstract Antimicrotubule drugs are used as chemotherapeutic agents due to their effects on essential cellular functions such as mitosis, organelle transport and maintenance of cell shape. When used in combination, paclitaxel with estramustine or vinblastine has demonstrated activity against hormone refractory prostate cancer. To understand the mechanism of resistance that develops in patients as a result of antimicrotubule drug therapy, we exposed human prostate carcinoma cells to IC20 and IC40 doses of estramustine, paclitaxel or vinblastine for 48 h and examined the β-tubulin (the cellular target) isotype composition. The results revealed an increase in the β III -tubulin isotype as a result of drug treatment both at protein and message levels. In addition, examination of human brain cell lines with different intrinsic levels of β III showed that cell lines with higher β III levels were more resistant to paclitaxel. These results are in agreement with our previous findings in human prostate carcinoma cell lines that were made resistant to estramustine or paclitaxel and suggest an important function for β III in antimicrotubule drug resistance. Also, the complete coding sequence of human β III tubulin reported here will provide molecular tools for future investigations.