Estramustine resistance correlates with tau over-expression in human prostatic carcinoma cells

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Estramustine (EM) is a key anti-microtubule drug for advanced prostate cancer.
• Microtubules are the primary targets of EM's cytotoxic effects.
• The role of microtubule-associated protein tau in EM resistance is not well understood.

Purpose of the Study:

• To investigate the effects of estramustine on the microtubule-associated protein tau.
• To determine tau's role in estramustine drug resistance in prostate cancer cells.

Main Methods:

• Comparison of tau expression in human prostate cancer cells (DU145) and an EM-resistant cell line (E4).
• Reverse transcriptase polymerase chain reaction (RT-PCR) to quantify tau mRNA levels.
• Western blotting to assess tau protein levels and phosphorylation status (including phosphotyrosine).

Main Results:

• Tau expression was 1.9-fold higher in EM-resistant E4 cells compared to DU145 cells at both mRNA and protein levels.
• Tau exhibited increased tyrosine phosphorylation in E4 cells and upon short-term EM exposure in DU145 cells.
• EM rapidly induced changes in tau's post-translational state, mirroring patterns seen in resistant cells.

Conclusions:

• Acquisition of EM resistance in prostate cancer cells involves significant alterations in tau expression and phosphorylation.
• Changes in tau, alongside tubulin modifications, contribute to estramustine drug resistance.
• Estramustine rapidly impacts tau's post-translational modification state, suggesting a dynamic role in drug response.