Abstract
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 β-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-µm (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 β-tubulin isotype-specific antibodies showed a ∼6-fold increase in the βIII-tubulin levels and moderate increase in overall β-tubulin levels in EM-resistant cells when compared to DU-145 cells. This increase of βIII isotype was confirmed by Western analysis. A reverse transcriptase-PCR assay was also employed using β-tubulin isotype-specific primers to quantify β-tubulin isotype RNA. A 4-fold increase in βIII and a 3-fold increase in βIVa transcript were seen in both EM-resistant cell lines. These results indicate that overexpression of specific β-tubulin isotypes may play a role in the cellular defense against EM and other antimicrotubule agents.
Footnotes
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↵1 This study was supported by an appropriation from the Commonwealth of Pennsylvania, CORE Grant NIH CA-06927, and Public Health Service Grant RO1 CA-57638 from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.
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↵2 To whom requests for reprints should be addressed, at Department of Medicine, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111. Phone: (215) 728-2542; Fax: (215) 728-4333.
- Received December 7, 1995.
- Accepted April 1, 1996.
- ©1996 American Association for Cancer Research.
Volume 56, Issue 11
