title: PTPL1 and PKCδ contribute to proapoptotic signalling in prostate cancer cells.
abstract: PTPL1 is a non-receptor protein tyrosine phosphatase involved in apoptosis regulation, although controversial findings have been reported in different cancer types. We report here a proapoptotic role for PTPL1 in PC3 and LNCaP prostate cancer cells, as its absence induces apoptosis resistance upon treatment with different drugs. In PC3 cells, PTPL1 silencing by small interfering RNA influences the expression levels of Bcl-xL and Mcl-1(S) proteins as well as final events in the apoptotic process such as activation of caspases and caspase-mediated cleavage of proteins like Mcl-1 or poly (ADP-ribose) polymerase. We have identified PKCδ as an intermediary of PTPL1-mediated apoptotic signalling and that phosphorylation status of NF-κB and IκBα is influenced by PTPL1 and PKCδ. Furthermore, the loss of PTPL1 and PKCδ expression in poorly differentiated, more aggressive human prostate cancers also indicate that their absence could be related to apoptosis resistance and tumour progression.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville 41013, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Castilla
authors.forename: D
authors.initials: D
authors.lastname: Chinchón
authors.forename: R
authors.initials: R
authors.lastname: Medina
authors.forename: F J
authors.initials: FJ
authors.lastname: Torrubia
authors.forename: M A
authors.initials: MA
authors.lastname: Japón
authors.forename: C
authors.initials: C
authors.lastname: Sáez
mesh_terms: D017209:Apoptosis; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051020:bcl-X Protein; D051550:I-kappa B Kinase; D051745:Protein Kinase C-delta; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13
references.citation: Oncogene. 2005 Jun 30;24(28):4486-95
references.pmid: 15856023
references.citation: Biochem J. 2004 Dec 15;384(Pt 3):449-59
references.pmid: 15491280
references.citation: Cell Death Differ. 2006 Aug;13(8):1263-7
references.pmid: 16676002
references.citation: J Biol Chem. 2008 Jun 13;283(24):16391-9
references.pmid: 18424438
references.citation: Biochem Biophys Res Commun. 2006 May 12;343(3):848-56
references.pmid: 16564022
references.citation: Prostate. 1998 Jul 1;36(2):92-101
references.pmid: 9655261
references.citation: Clin Cancer Res. 1997 Jun;3(6):963-72
references.pmid: 9815772
references.citation: J Biol Chem. 2005 Nov 25;280(47):38982-91
references.pmid: 16183650
references.citation: Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):260-6
references.pmid: 14734478
references.citation: Cancer Res. 2002 Jul 1;62(13):3615-9
references.pmid: 12097262
references.citation: EMBO J. 1998 Mar 16;17(6):1675-87
references.pmid: 9501089
references.citation: Virchows Arch. 2006 Feb;448(2):111-8
references.pmid: 16328356
references.citation: Cancer Res. 2007 Jul 15;67(14):6806-13
references.pmid: 17638892
references.citation: Endocrinology. 2006 Oct;147(10):4960-7
references.pmid: 16794010
references.citation: Prostate. 2002 Jun 1;51(4):231-40
references.pmid: 11987151
references.citation: Eur J Biochem. 2000 Dec;267(24):7170-5
references.pmid: 11106428
references.citation: J Cell Biochem. 2004 Jan 1;91(1):100-17
references.pmid: 14689584
references.citation: Prostate Cancer Prostatic Dis. 2005;8(2):108-18
references.pmid: 15724144
references.citation: Cancer Res. 1997 May 1;57(9):1758-68
references.pmid: 9135020
references.citation: J Gastroenterol Hepatol. 2006 Jan;21(1 Pt 1):84-91
references.pmid: 16706817
references.citation: Clin Cancer Res. 2005 Apr 1;11(7):2670-9
references.pmid: 15814648
references.citation: Carcinogenesis. 2004 May;25(5):765-72
references.pmid: 14729592
references.citation: FASEB J. 2004 Apr;18(6):627-36
references.pmid: 15054085
references.citation: Prostate. 2007 Nov 1;67(15):1641-53
references.pmid: 17823925
references.citation: Int J Biochem Cell Biol. 2005 Apr;37(4):707-14
references.pmid: 15694830
references.citation: Mol Cancer Ther. 2004 May;3(5):567-75
references.pmid: 15141014
references.citation: Am J Pathol. 1999 Jan;154(1):137-44
references.pmid: 9916928
references.citation: J Cell Sci. 2002 Dec 15;115(Pt 24):4843-53
references.pmid: 12432072
references.citation: Cancer Biol Ther. 2005 Apr;4(4):382-90
references.pmid: 15846101
references.citation: J Clin Invest. 2002 Mar;109(6):827-36
references.pmid: 11901191
references.citation: Cancer Res. 2007 Nov 15;67(22):10859-68
references.pmid: 18006831
references.citation: Int J Cancer. 2009 Feb 1;124(3):638-43
references.pmid: 19004008
references.citation: Phytochemistry. 2001 Jan;56(1):5-51
references.pmid: 11198818
references.citation: J Biol Chem. 2002 Dec 6;277(49):47861-9
references.pmid: 12354757
references.citation: Cancer Metastasis Rev. 2008 Jun;27(2):205-14
references.pmid: 18265946
references.citation: Carcinogenesis. 2006 Nov;27(11):2223-34
references.pmid: 16774948
references.citation: J Biol Chem. 2006 Apr 28;281(17):12102-11
references.pmid: 16505477