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Ranganathan S , Dexter DW , Benetatos CA , Hudes GR
Cloning and sequencing of human beta(III)-tubulin cDNA: induction of beta(III) isotype in human prostate carcinoma cells by acute exposure to antimicrotubule agents
Biochimica Et Biophysica Acta-Gene Structure and Expression. 1998 Jan 21;1395(2) :237-245
AbstractAntimicrotubule 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 P-tubulin (the cellular target) isotype composition. The results revealed an increase in the beta(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 beta(III) showed that cell lines with higher beta(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 beta(III) in antimicrotubule drug resistance. Also, the complete coding sequence of human beta(III) tubulin reported here will provide molecular tools for future investigations. (C) 1998 Elsevier Science B.V.
NotesTimes Cited: 12 English Article YW341 BBA-GENE STRUCT EXPRESS