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

J Cell Biochem. 2009 Oct 15;108(3):555-64. doi: 10.1002/jcb.22287.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cytoskeleton / metabolism
  • Humans
  • Male
  • Microtubules / metabolism
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / metabolism*
  • Protein Binding
  • Protein Isoforms / metabolism
  • Protein Transport
  • tau Proteins / metabolism*

Substances

  • Protein Isoforms
  • tau Proteins
  • Phosphatidylinositol 3-Kinases

Associated data

  • GENBANK/FJ429137