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Microtubule‐associated protein tau in human prostate cancer cells: Isoforms, phosphorylation, and interactions
Author(s) -
Souter Skye,
Lee Gloria
Publication year - 2009
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22287
Subject(s) - gene isoform , microtubule , kinase , exon , prostate cancer , phosphorylation , alternative splicing , biology , tau protein , protein subunit , microbiology and biotechnology , cancer research , chemistry , alzheimer's disease , cancer , gene , biochemistry , medicine , disease , genetics
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. J. Cell. Biochem. 108: 555–564, 2009. © 2009 Wiley‐Liss, Inc.