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Microtubule-associated protein tau in human prostate cancer cells: isoforms, phosphorylation, and interactions
Journal article   Peer reviewed

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

Skye Souter and Gloria Lee
Journal of cellular biochemistry, Vol.108(3), pp.555-564
10/15/2009
DOI: 10.1002/jcb.22287
PMCID: PMC4299866
PMID: 19681044

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Abstract

Tau is a microtubule-associated protein whose function has been investigated primarily in neurons. Recently, tau expression has been correlated with increased drug resistance in various cancers of non-neuronal tissues. In this report, we investigate the tau expressed in cancerous prostate lines ALVA-31, DU 145, and PC-3. Prostate cancer tau is heat-stable and highly phosphorylated, containing many of the modifications identified in Alzheimer's disease brain tau. RT-PCR and phosphatase treatment indicated that all six alternatively spliced adult brain tau isoforms are expressed in ALVA-31 cells, and isoforms containing exon 6 as well as high molecular weight tau isoforms containing either exon 4A or a larger splice variant of exon 4A are also present. 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. Finally, endogenous ALVA-31 tau can interact with the p85 subunit of phosphatidylinositol 3-kinase, as demonstrated by co-immunoprecipitations and in vitro protein-binding assays. Our results suggest that tau in prostate cancer cells does not resemble that from normal adult brain and support the hypothesis that tau is a multifunctional protein.
Prostatic Neoplasms - metabolism Phosphorylation Humans Molecular Sequence Data tau Proteins - metabolism Male Phosphatidylinositol 3-Kinases - metabolism Protein Transport Microtubules - metabolism Protein Isoforms - metabolism Cell Line, Tumor Cytoskeleton - metabolism Prostatic Neoplasms - enzymology Protein Binding Adult

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