Normal and prostate cancer cells display distinct molecular profiles of alpha-tubulin posttranslational modifications.

Multiple diverse posttranslational modifications of alpha-tubulin such as detyrosination, further cleavage of the penultimate glutamate residue (Delta2-tubulin), acetylation, and polyglutamylation increase the structural and functional diversity of microtubules. Herein, we characterized the molecular profile of alpha-tubulin posttranslational modifications in normal human prostate epithelial cells (PrEC), immortalized normal prostate epithelial cells (PZ-HPV-7), androgen-dependent prostate cancer cells (LNCaP), transitional androgen-independent prostate cancer cells (LNCaP-cds and CWR22Rv1), and androgen-independent prostate cancer cells (PC3). Compared to PrEC and PZ-HPV-7 cells, all cancer cells exhibited elevated levels of detyrosinated and polyglutamylated alpha-tubulin, that was paralleled by decreased protein levels of tubulin tyrosine ligase (TTL). In contrast, PrEC and PZ-HPV-7 cells expressed markedly higher levels of Delta2-tubulin. Whereas alpha-tubulin acetylation levels were generally equivalent in all the cell lines, PC3 cells did not display detectable levels of Ac-tubulin. These data may reveal novel biomarkers of prostate cancer and new therapeutic targets.