title: Protein interacting with C alpha kinase 1 (PICK1) is involved in promoting tumor growth and correlates with poor prognosis of human breast cancer.
abstract: Protein interacting with C alpha kinase 1 (PICK1), which interacts with multiple different proteins in a variety of cellular contexts, is believed to play important roles in diverse pathological conditions including cancer. In this study, we attempted to investigate the correlation of PICK1 with clinicopathological features as well as prognosis of human breast cancer. In addition, we aimed at a better understanding of the biological function of PICK1 in breast cancer cell biology. As judged by semi- quantitative RT-PCR and western blotting, PICK1 was overexpressed in tumor cells as compared to adjacent normal epithelia in breast, lung, gastric, colorectal, and ovarian cancer. As judged by immunostaining breast cancer tissue microarrays, high levels of PICK1 expression correlated with shortened span of overall survival (OS). Protein interacting with C alpha kinase 1 (PICK1) expression seemed to be specifically associated with reduced OS in lymph node-positive, Her/neu-2 positive, and the basal-like type subgroups, respectively. Consistently, the expression of PICK1 correlated with histological grade, lymph node metastasis, Her-2/neu-positivity, and triple-negative basal-like breast cancer. Protein interacting with C alpha kinase 1 (PICK1) was not correlated with menopausal status, tumor size, or hormone receptor status. In a complementary study, transfection of MDA-MB-231 cells with PICK1 siRNA decreased cell proliferation and colony formation in vitro and inhibited tumorigenicity in nude mice. Our clinical and experimental evidence supports an oncogenic role of PICK1 in human breast cancer. In particular, our data suggest that PICK1 promotes tumor cell proliferation. Taken together, PICK1 may serve not only as a marker for poor prognosis, but also as a therapeutic target in breast cancer.
authors.affiliation: National Key Laboratory of Breast Cancer Prevention and Treatment, Tianjin Medical University, Tianjin, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Cao
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Ruifang
authors.initials: R
authors.lastname: Niu
authors.forename: Yun
authors.initials: Y
authors.lastname: Niu
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
authors.forename: Xuchen
authors.initials: X
authors.lastname: Cao
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D012189:Retrospective Studies; D023041:Xenograft Model Antitumor Assays
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; C498297:PICk1 protein, human
references.citation: Biochem J. 2001 Mar 15;354(Pt 3):635-43
references.pmid: 11237868
references.citation: Eur J Surg Oncol. 2007 May;33(4):409-19
references.pmid: 17125963
references.citation: Lancet Oncol. 2007 Mar;8(3):235-44
references.pmid: 17329194
references.citation: Lancet. 2005 May 14-20;365(9472):1687-717
references.pmid: 15894097
references.citation: Mol Pharmacol. 2001 Nov;60(5):916-23
references.pmid: 11641419
references.citation: Anal Cell Pathol. 1999;19(2):53-8
references.pmid: 10746434
references.citation: J Neurosci. 2000 Oct 1;20(19):7252-7
references.pmid: 11007882
references.citation: Nat Rev Drug Discov. 2004 Dec;3(12):1047-56
references.pmid: 15573103
references.citation: J Cancer Educ. 2006 Spring;21(1 Suppl):S69-79
references.pmid: 17020506
references.citation: Virchows Arch. 2008 Aug;453(2):123-32
references.pmid: 18677512
references.citation: Future Oncol. 2008 Apr;4(2):271-87
references.pmid: 18407739
references.citation: Neuron. 2003 Feb 20;37(4):625-38
references.pmid: 12597860
references.citation: Biochem J. 2002 Feb 1;361(Pt 3):443-50
references.pmid: 11802773
references.citation: Curr Opin Obstet Gynecol. 2008 Feb;20(1):40-6
references.pmid: 18197004
references.citation: Neuron. 2003 Jan 23;37(2):263-74
references.pmid: 12546821
references.citation: Lancet. 1999 May 15;353(9165):1641-8
references.pmid: 10335782
references.citation: Histopathology. 2008 Jan;52(1):108-18
references.pmid: 18171422
references.citation: Neuron. 2001 Apr;30(1):121-34
references.pmid: 11343649
references.citation: Breast Cancer Res Treat. 2008 Feb;107(3):309-30
references.pmid: 17377838
references.citation: Ann Oncol. 2007 Aug;18(8):1293-306
references.pmid: 17317675
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):4029-34
references.pmid: 9520487
references.citation: Neuron. 2000 Nov;28(2):485-97
references.pmid: 11144358
references.citation: Nutr Rev. 2008 Aug;66(8):477-82
references.pmid: 18667010
references.citation: Adv Exp Med Biol. 2007;608:1-22
references.pmid: 17993229
references.citation: J Biol Chem. 2002 Dec 27;277(52):50463-8
references.pmid: 12399460
references.citation: Nature. 1996 Feb 15;379(6566):606-12
references.pmid: 8628395
references.citation: J Cell Sci. 2004 Sep 1;117(Pt 19):4401-9
references.pmid: 15304526
references.citation: Neuron. 1999 Jan;22(1):179-87
references.pmid: 10027300
references.citation: Clin Cancer Res. 2008 Aug 1;14(15):4898-907
references.pmid: 18676764
references.citation: J Biol Chem. 2001 May 4;276(18):15256-63
references.pmid: 11278603
references.citation: J Biol Chem. 2002 Feb 15;277(7):5203-8
references.pmid: 11739374
references.citation: J Clin Oncol. 2006 May 10;24(14):2137-50
references.pmid: 16682732
references.citation: J Biol Chem. 1997 Dec 19;272(51):32019-24
references.pmid: 9405395
references.citation: BMC Cancer. 2008 Mar 28;8:83
references.pmid: 18373849
references.citation: J Clin Oncol. 2008 May 20;26(15):2568-81
references.pmid: 18487574
references.citation: Am J Health Syst Pharm. 2008 Jan 1;65(1):23-8
references.pmid: 18159035
references.citation: Cancer Res. 2007 Jun 1;67(11):5308-17
references.pmid: 17545611
references.citation: J Clin Oncol. 2007 Jan 1;25(1):118-45
references.pmid: 17159189
references.citation: Histopathology. 2008 Jan;52(1):82-90
references.pmid: 18171419
references.citation: Annu Rev Pharmacol Toxicol. 2003;43:261-84
references.pmid: 12359863
references.citation: Ann Surg Oncol. 2007 Sep;14(9):2502-9
references.pmid: 17564750
references.citation: N Engl J Med. 2005 Oct 27;353(17):1784-92
references.pmid: 16251534
references.citation: J Clin Pathol. 2004 Jul;57(7):675-81
references.pmid: 15220356
references.citation: J Cell Biol. 1995 Feb;128(3):263-71
references.pmid: 7844141