title: Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer.
abstract: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a 7-transmembrane receptor reportedly expressed in stem cells of the intestinal crypts and hair follicles of mice. Overexpression of LGR5 is observed in some types of cancer; however, there has been no specific assessment in colorectal tumorigenesis. We performed quantitative RT-PCR for LGR5 expression in 37 representative cancer cell lines, and showed that LGR5 mRNA was frequently overexpressed in colon cancer cell lines. Moreover, LGR5 expression was higher in colon cancer cell lines derived from metastatic tumors compared with those from primary tumors. In clinical specimens, there was significant overexpression of LGR5 in 35 of 50 colorectal cancers (CRCs), and in seven of seven sporadic colonic adenomas, compared with matched normal mucosa. This suggests up-regulation of LGR5 from the early stage of colorectal tumorigenesis. LGR5 expression showed marked variation among CRC cases and correlated significantly with lymphatic invasion, vascular invasion, tumor depth, lymph node metastasis, and tumor stage (IIIC vs. IIIB). In addition to cancer cells, crypt base columnar cells of the small intestine and colon were shown by in situ hybridization to express LGR5. This is the first report suggesting the involvement of LGR5, not only in early events but also in late events in colorectal tumorigenesis.
authors.affiliation: Department of Pathology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchida
authors.forename: Ken
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Mariko
authors.initials: M
authors.lastname: Fukuma
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hayashida
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
mesh_terms: D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007930:Leucine / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: C116884:LGR5 protein, human; C493597:Lgr5 protein, mouse; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D043562:Receptors, G-Protein-Coupled; D007930:Leucine
references.citation: Mol Cell Biol. 2004 Nov;24(22):9736-43
references.pmid: 15509778
references.citation: Mol Endocrinol. 1998 Dec;12(12):1830-45
references.pmid: 9849958
references.citation: Hepatology. 2003 Mar;37(3):528-33
references.pmid: 12601349
references.citation: Am J Med. 1994 Nov;97(5):418-28
references.pmid: 7977430
references.citation: Hum Mol Genet. 2008 Dec 15;17(24):3864-75
references.pmid: 18782851
references.citation: Mol Endocrinol. 2002 Jun;16(6):1135-44
references.pmid: 12040002
references.citation: Hum Cell. 2005 Sep;18(3):143-6
references.pmid: 17022146
references.citation: J Natl Cancer Inst. 2004 Oct 6;96(19):1420-5
references.pmid: 15467030
references.citation: Gastroenterology. 2007 Feb;132(2):628-32
references.pmid: 17320548
references.citation: Science. 1997 Mar 21;275(5307):1784-7
references.pmid: 9065401
references.citation: Ann Med. 2002;34(7-8):554-64
references.pmid: 12553495
references.citation: Trends Pharmacol Sci. 2003 Jan;24(1):30-5
references.pmid: 12498728
references.citation: Cell. 1996 Oct 18;87(2):159-70
references.pmid: 8861899
references.citation: Gynecol Oncol. 2004 Sep;94(3):643-9
references.pmid: 15350353
references.citation: Br J Clin Pharmacol. 2004 Apr;57(4):373-87
references.pmid: 15025734
references.citation: Clin Ther. 2006 Oct;28(10):1485-508
references.pmid: 17157109
references.citation: J Clin Oncol. 2007 Jun 20;25(18):2509-15
references.pmid: 17577027
references.citation: Nat Genet. 2008 Nov;40(11):1291-9
references.pmid: 18849992
references.citation: Curr Opin Drug Discov Devel. 2001 Sep;4(5):535-47
references.pmid: 12825450
references.citation: Nature. 2009 Jan 29;457(7229):608-11
references.pmid: 19092804
references.citation: Cell. 2002 Oct 18;111(2):241-50
references.pmid: 12408868
references.citation: Am J Pathol. 2008 Sep;173(3):835-43
references.pmid: 18688030
references.citation: Science. 1997 Mar 21;275(5307):1787-90
references.pmid: 9065402
references.citation: N Engl J Med. 1988 Sep 1;319(9):525-32
references.pmid: 2841597
references.citation: Curr Opin Pharmacol. 2003 Apr;3(2):140-5
references.pmid: 12681235
references.citation: Nature. 2007 Oct 25;449(7165):1003-7
references.pmid: 17934449
references.citation: Mol Cell Endocrinol. 1999 May 25;151(1-2):181-93
references.pmid: 10411333
references.citation: Lancet. 2007 May 19;369(9574):1711-23
references.pmid: 17512856
references.citation: Biochem Biophys Res Commun. 1998 Jun 18;247(2):266-70
references.pmid: 9642114
references.citation: CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
references.pmid: 17237035
references.citation: Gynecol Oncol. 1987 Mar;26(3):340-54
references.pmid: 2435620