title: Microtubule-associated protein tau in human prostate cancer cells: isoforms, phosphorylation, and interactions.
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.
authors.affiliation: Program in Molecular and Cellular Biology, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Skye
authors.initials: S
authors.lastname: Souter
authors.forename: Gloria
authors.initials: G
authors.lastname: Lee
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008297:Male; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins; D019869:Phosphatidylinositol 3-Kinases
references.citation: Cell Cycle. 2005 Sep;4(9):1149-52
references.pmid: 16103753
references.citation: J Neurochem. 2007 Jan;100(2):437-45
references.pmid: 17144905
references.citation: J Cell Sci. 1998 May;111 ( Pt 10):1419-32
references.pmid: 9570759
references.citation: J Cell Sci. 2004 Nov 15;117(Pt 24):5721-9
references.pmid: 15537830
references.citation: J Neuropathol Exp Neurol. 1996 Jul;55(7):774-86
references.pmid: 8965093
references.citation: Cell Mol Life Sci. 2007 Sep;64(17):2219-33
references.pmid: 17604998
references.citation: J Cell Sci. 1998 Nov;111 ( Pt 21):3167-77
references.pmid: 9763511
references.citation: Proc Natl Acad Sci U S A. 1992 May 15;89(10):4378-81
references.pmid: 1374898
references.citation: J Cell Biochem. 2004 Apr 1;91(5):880-95
references.pmid: 15034924
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8315-20
references.pmid: 15914550
references.citation: Cancer Res. 1997 May 1;57(9):1758-68
references.pmid: 9135020
references.citation: Br J Cancer. 2006 Jun 19;94(12):1894-7
references.pmid: 16721363
references.citation: Neuron. 1993 Jul;11(1):153-63
references.pmid: 8393323
references.citation: FEBS Lett. 1995 Nov 20;375(3):243-8
references.pmid: 7498509
references.citation: Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1983-7
references.pmid: 1542696
references.citation: J Biol Chem. 2008 Jun 27;283(26):18177-86
references.pmid: 18467332
references.citation: J Biol Chem. 2007 Apr 20;282(16):12230-9
references.pmid: 17307736
references.citation: J Cell Biol. 1985 Oct;101(4):1371-8
references.pmid: 3930508
references.citation: Neurobiol Aging. 2000 Nov-Dec;21(6):815-28
references.pmid: 11124425
references.citation: J Neurochem. 1998 Apr;70(4):1346-56
references.pmid: 9523550
references.citation: Biochim Biophys Acta. 2005 Jan 3;1739(2-3):91-103
references.pmid: 15615629
references.citation: J Biol Chem. 1992 Jan 5;267(1):564-9
references.pmid: 1370450
references.citation: Mol Cancer Ther. 2007 May;6(5):1509-16
references.pmid: 17483439
references.citation: J Alzheimers Dis. 2003 Apr;5(2):65-77
references.pmid: 12719624
references.citation: Methods Enzymol. 1986;134:89-104
references.pmid: 3821583
references.citation: Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10369-73
references.pmid: 7479786
references.citation: J Biol Chem. 1995 Aug 11;270(32):18917-22
references.pmid: 7642549
references.citation: Muscle Nerve. 1999 Jan;22(1):61-70
references.pmid: 9883858
references.citation: Neurosci Lett. 2000 Jun 30;287(3):187-90
references.pmid: 10863026
references.citation: Oncogene. 1991 Jun;6(6):1085-7
references.pmid: 1829806
references.citation: Methods Enzymol. 1986;134:104-15
references.pmid: 2881188
references.citation: Chromosoma. 1996 Jul;105(1):20-30
references.pmid: 8662255
references.citation: Exp Neurol. 2002 Oct;177(2):475-93
references.pmid: 12429193
references.citation: J Cell Sci. 1992 Jun;102 ( Pt 2):227-37
references.pmid: 1400630
references.citation: Mol Biol Cell. 1995 Oct;6(10):1397-410
references.pmid: 8573794
references.citation: Proc Natl Acad Sci U S A. 1975 May;72(5):1858-62
references.pmid: 1057175
references.citation: Biochim Biophys Acta. 2005 Jan 3;1739(2-3):268-79
references.pmid: 15615645
references.citation: Acta Neuropathol. 1999 Sep;98(3):251-6
references.pmid: 10483782
references.citation: J Neurosci. 2004 Mar 3;24(9):2304-12
references.pmid: 14999081
references.citation: J Neurochem. 1996 Sep;67(3):1235-44
references.pmid: 8752131
references.citation: Biochim Biophys Acta. 2007 Apr;1772(4):457-66
references.pmid: 17158035
references.citation: Int J Cancer. 1998 Aug 12;77(4):626-31
references.pmid: 9679768
references.citation: Acta Neuropathol. 1992;84(3):265-72
references.pmid: 1384266
references.citation: Acta Neuropathol. 2002 Jan;103(1):26-35
references.pmid: 11837744
references.citation: Biol Reprod. 1992 Jan;46(1):120-9
references.pmid: 1547309
references.citation: J Neurosci Res. 1994 Dec 15;39(6):669-73
references.pmid: 7534834
references.citation: Mol Biol Cell. 2000 Dec;11(12):4093-104
references.pmid: 11102510
references.citation: J Cell Biochem. 2000 May;78(2):305-17
references.pmid: 10842324
references.citation: Biochemistry. 1992 Nov 3;31(43):10626-33
references.pmid: 1420178
references.citation: J Neurosci Res. 2008 Sep;86(12):2763-73
references.pmid: 18500754