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Ranganathan S , Dexter DW , Benetatos CA , Chapman AE , Tew KD , Hudes GR
Increase of beta(III)- and beta(IVa)-tubulin isotypes in human prostate carcinoma cells as a result of estramustine resistance
Cancer Research. 1996 Jun 1;56(11) :2584-2589
AbstractEstramustine (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 of drugs, human prostate carcinoma cells (DU-145) were made resistant to EM, and two cell lines were selected at 12- (EM- 12) and 15-mu M (EM-15) concentrations of the drug, These cell lines exhibited 8- to 9-fold resistance to EM and 2- to 4-fold cross-resistance to paclitaxel, Immunofluorescent staining of the cells with beta-tubulin isotype-specific antibodies showed a similar to 6-fold increase in the beta(III)-tubulin levels and moderate increase in overall beta-tubulin levels in EM- resistant cells when compared to DU-145 cells, This increase of beta(III) isotype was confirmed by Western analysis, A reverse transcriptase-PCR assay was also employed using beta-tubulin isotype-specific primers to quantify beta-tubulin isotype RNA, A 4-fold increase in beta(III) and a 3-fold increase in beta(IVa) transcript were seen in both EM-resistant cell lines, These results indicate that overexpression of specific beta- tubulin isotypes may play a role in the cellular defense against EM and other antimicrotubule agents.
NotesTimes Cited: 48 English Article UN250 CANCER RES