title: Altered RECQ Helicase Expression in Sporadic Primary Colorectal Cancers.
abstract: Deregulation of DNA repair enzymes occurs in cancers and may create a susceptibility to chemotherapy. Expression levels of DNA repair enzymes have been shown to predict the responsiveness of cancers to certain chemotherapeutic agents. The RECQ helicases repair damaged DNA including damage caused by topoisomerase I inhibitors, such as irinotecan. Altered expression levels of these enzymes in colorectal cancer (CRC) may influence the response of the cancers to irinotecan. Thus, we assessed RECQ helicase (WRN, BLM, RECQL, RECQL4, and RECQL5) expression in primary CRCs, matched normal colon, and CRC cell lines. We found that BLM and RECQL4 mRNA levels are significantly increased in CRC (P = .0011 and P < .0001, respectively), whereas RECQL and RECQL5 are significantly decreased (P = .0103 and P = .0029, respectively). RECQ helicase expression patterns varied between specific molecular subtypes of CRCs. The mRNA and protein expression of the majority of the RECQ helicases was closely correlated, suggesting that altered mRNA expression is the predominant mechanism for deregulated RECQ helicase expression. Immunohistochemistry localized the RECQ helicases to the nucleus. RECQ helicase expression is altered in CRC, suggesting that RECQ helicase expression has potential to identify CRCs that are susceptible to specific chemotherapeutic agents.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA ; Department of Surgery, University of Washington Medical School, Seattle, WA ; Department of Surgery, University of Nebraska Medical School, Omaha, NE.
authors.forename: Victoria Valinluck
authors.initials: VV
authors.lastname: Lao
authors.forename: Piri
authors.initials: P
authors.lastname: Welcsh
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Luo
authors.forename: Kelly T
authors.initials: KT
authors.lastname: Carter
authors.forename: Slavomir
authors.initials: S
authors.lastname: Dzieciatkowski
authors.forename: Suzanne
authors.initials: S
authors.lastname: Dintzis
authors.forename: Jane
authors.initials: J
authors.lastname: Meza
authors.forename: Nora E
authors.initials: NE
authors.lastname: Sarvetnick
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Monnat
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Loeb
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
references.citation: J Mol Cell Biol. 2011 Feb;3(1):31-8
references.pmid: 21278449
references.citation: Mol Biol Cell. 2009 Jan;20(1):114-23
references.pmid: 18987339
references.citation: Cancer Epidemiol Biomarkers Prev. 2012 Mar;21(3):411-6
references.pmid: 22219318
references.citation: Cancer Res. 2010 Aug 15;70(16):6548-55
references.pmid: 20663905
references.citation: Science. 2002 Sep 20;297(5589):2051-3
references.pmid: 12242442
references.citation: J Clin Oncol. 2009 Apr 10;27(11):1814-21
references.pmid: 19273709
references.citation: Trends Biochem Sci. 2008 Dec;33(12):609-20
references.pmid: 18926708
references.citation: Biochem J. 2008 Jun 15;412(3):425-33
references.pmid: 18290761
references.citation: Nat Rev Cancer. 2008 Mar;8(3):193-204
references.pmid: 18256616
references.citation: Mol Cell Biol. 2007 Mar;27(5):1784-94
references.pmid: 17158923
references.citation: Lancet. 2002 Nov 2;360(9343):1381-91
references.pmid: 12423985
references.citation: DNA Repair (Amst). 2012 Jun 1;11(6):537-49
references.pmid: 22542292
references.citation: Clin Cancer Res. 2010 Dec 15;16(24):6159-68
references.pmid: 20802015
references.citation: DNA Repair (Amst). 2010 Mar 2;9(3):345-53
references.pmid: 20080450
references.citation: Neoplasia. 2009 Mar;11(3):260-8, 3p following 268
references.pmid: 19242607
references.citation: Cell Cycle. 2012 Nov 15;11(22):4252-65
references.pmid: 23095637
references.citation: Annu Rev Genet. 2002;36:617-56
references.pmid: 12429704
references.citation: DNA Repair (Amst). 2010 Mar 2;9(3):315-24
references.pmid: 20061189
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Nat Rev Clin Oncol. 2012 Feb 14;9(3):144-55
references.pmid: 22330686
references.citation: Cytometry. 1994 Sep 1;17(1):66-74
references.pmid: 8001459
references.citation: World J Gastroenterol. 2010 Mar 28;16(12):1482-6
references.pmid: 20333788
references.citation: Semin Cancer Biol. 2010 Oct;20(5):279-80
references.pmid: 20937389
references.citation: Nucleic Acids Res. 2006;34(18):5217-31
references.pmid: 17003056
references.citation: Oncogene. 2002 Dec 16;21(58):9008-21
references.pmid: 12483516
references.citation: Cancer Res. 2010 Nov 15;70(22):9207-17
references.pmid: 21045146
references.citation: N Engl J Med. 2009 Jul 9;361(2):123-34
references.pmid: 19553641
references.citation: Biochem J. 2008 Jun 1;412(2):299-306
references.pmid: 18215118
references.citation: Prog Nucleic Acid Res Mol Biol. 2006;81:179-229
references.pmid: 16891172
references.citation: Biosci Rep. 2011 Oct;31(5):363-9
references.pmid: 21210765
references.citation: Mol Biol Cell. 2012 Nov;23(21):4273-85
references.pmid: 22973052
references.citation: Mech Ageing Dev. 2008 Jan-Feb;129(1-2):79-90
references.pmid: 18054793
references.citation: Oncogene. 2013 Apr 18;32(16):2037-47
references.pmid: 22751117
references.citation: Eur J Histochem. 1998;42(1):41-8
references.pmid: 9615190
references.citation: N Engl J Med. 2003 Jul 17;349(3):247-57
references.pmid: 12867608
references.citation: Cancer Res. 1999 Jan 15;59(2):320-4
references.pmid: 9927040
references.citation: Cell Cycle. 2008 Mar 15;7(6):796-807
references.pmid: 18250621
references.citation: DNA Repair (Amst). 2008 Nov 1;7(11):1776-86
references.pmid: 18722555
references.citation: Mutat Res. 2012 Aug 1;736(1-2):15-24
references.pmid: 21689668
references.citation: Gastroenterology. 2008 May;134(5):1296-310
references.pmid: 18471507
references.citation: Genes Dev. 2007 Dec 1;21(23):3073-84
references.pmid: 18003859
references.citation: J Biol Chem. 2010 May 21;285(21):15739-45
references.pmid: 20348101
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Surg Oncol Clin N Am. 2010 Oct;19(4):819-27
references.pmid: 20883956
references.citation: Nat Rev Mol Cell Biol. 2010 Mar;11(3):171-81
references.pmid: 20125188
references.citation: J Cell Biochem. 2010 Jan 1;109(1):7-15
references.pmid: 19911388
references.citation: Nucleic Acids Res. 2012 Aug;40(14):6632-48
references.pmid: 22544709
references.citation: Pituitary. 1999 May;1(3-4):147-51
references.pmid: 11081192
references.citation: Semin Cancer Biol. 2010 Oct;20(5):329-39
references.pmid: 20934517
references.citation: Nat Genet. 2006 Jul;38(7):787-93
references.pmid: 16804544
references.citation: Mod Pathol. 1998 Feb;11(2):155-68
references.pmid: 9504686
references.citation: Biochem J. 2006 Sep 15;398(3):319-37
references.pmid: 16925525