Microtubule-associated protein tau in human prostate cancer cells: Isoforms, phosphorylation, and interactions

Tau is a microtubule-associated protein expressed primarily in neurons. While it has been established that tau is expressed in additional cell types, its function in non-neuronal cells is unclear. Recently, tau expression has been correlated with drug resistance in various cancers. In this work, we investigate tau expression in cancerous prostate lines ALVA-31, DU 145, LNCaP, and PC-3. Prostate cancer tau is heat-stable and highly phosphorylated, featuring many of the modifications identified in Alzheimer's Disease brain tau. RT-PCR and phosphatase treatment suggest that all six alternatively spliced adult brain tau isoforms are expressed in ALVA-31 cells, and that isoforms containing exon 6+ are present. High molecular weight tau isoforms containing either exon 4A or a larger splice variant of exon 4A are also expressed. Consistent with its hyperphosphorylated state, a large proportion of ALVA-31 tau does not bind to microtubules, as detected by confocal microscopy and biochemical tests. Endogenous ALVA-31 tau can interact with the SH3 domains of both Fyn and the p85 subunit of PI3K, as demonstrated by in vitro fusion protein binding assays. Finally, co-immunoprecipitations demonstrate that tau and PI3K p85 interact in both stably-transfected SH-SY5Y cells and ALVA-NEO cells.