Increase of βIII- and βIVa-Tubulin Isotypes in Human Prostate Carcinoma Cells as a Result of Estramustine Resistance

作者: Gary R. Hudes , Kenneth D. Tew , Sulabha Ranganathan , Andrew E. Chapman , Dwayne W. Dexter

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摘要: Estramustine (EM), an antimicrotubule agent, is effective against hormone-refractory prostate cancer when used in combination with vinblastine or paclitaxel. To understand the effect of EM on beta-tubulin, a cellular target for this class drugs, human carcinoma cells (DU-145) were made resistant to EM, and two cell lines selected at 12- (EM-12) 15-microMolar (EM-15) concentrations drug. These exhibited 8- 9-fold resistance 2- 4-fold cross-resistance Immunofluorescent staining beta-tubulin isotype-specific antibodies showed approximately 6-fold increase beta(III)-tubulin levels moderate overall EM-resistant compared DU-145 cells. This beta(III) isotype was confirmed by Western analysis. A reverse transcriptase-PCR assay also employed using primers quantify RNA. 3-fold beta(IV alpha) transcript seen both lines. results indicate that overexpression specific isotypes may play role defense other agents.

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