title: The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma.
abstract: The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA) remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE), and normal esophagus (NE) using immunohistochemistry (IHC) and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100%) EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2-overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted.
authors.affiliation: Department of Surgery, University of Pittsburgh and the Hillman Cancer Center, Pittsburgh, PA 15261, USA.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Herrera
authors.forename: Talal
authors.initials: T
authors.lastname: El-Hefnawy
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Queiroz de Oliveira
authors.forename: Siva
authors.initials: S
authors.lastname: Raja
authors.forename: Sydney
authors.initials: S
authors.lastname: Finkelstein
authors.forename: William
authors.initials: W
authors.lastname: Gooding
authors.forename: James D
authors.initials: JD
authors.lastname: Luketich
authors.forename: Tony E
authors.initials: TE
authors.lastname: Godfrey
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hughes
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D019014:fas Receptor; D017228:Hepatocyte Growth Factor; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019859:Proto-Oncogene Proteins c-met
references.citation: Am J Gastroenterol. 2001 Apr;96(4):990-6
references.pmid: 11316217
references.citation: Oncogene. 2000 Nov 20;19(49):5582-9
references.pmid: 11114738
references.citation: Clin Cancer Res. 2001 Dec;7(12):4041-8
references.pmid: 11751499
references.citation: Int J Cancer. 2002 Mar 1;98(1):8-13
references.pmid: 11857377
references.citation: Mol Cell. 2002 Feb;9(2):411-21
references.pmid: 11864613
references.citation: Am J Pathol. 2002 Mar;160(3):963-72
references.pmid: 11891194
references.citation: J Natl Cancer Inst. 2002 Mar 20;94(6):406-7
references.pmid: 11904306
references.citation: Anticancer Res. 2001 Nov-Dec;21(6A):3813-20
references.pmid: 11911252
references.citation: Cancer Res. 2003 Sep 1;63(17):5462-9
references.pmid: 14500382
references.citation: Biochem Biophys Res Commun. 1984 Aug 16;122(3):1450-9
references.pmid: 6477569
references.citation: Cancer Res. 1989 Jun 15;49(12):3314-20
references.pmid: 2524251
references.citation: J Cell Biol. 1990 Nov;111(5 Pt 1):2097-108
references.pmid: 2146276
references.citation: Science. 1991 Feb 15;251(4995):802-4
references.pmid: 1846706
references.citation: JAMA. 1991 Mar 13;265(10):1287-9
references.pmid: 1995976
references.citation: Cancer Cells. 1991 Jun;3(6):227-32
references.pmid: 1832923
references.citation: Mol Cell Biol. 1992 Nov;12(11):5152-8
references.pmid: 1406687
references.citation: JAMA. 1993 Sep 15;270(11):1320
references.pmid: 8360967
references.citation: Symp Soc Exp Biol. 1993;47:163-81
references.pmid: 8165564
references.citation: Cancer Res. 1995 May 1;55(9):1963-70
references.pmid: 7728766
references.citation: Cancer Lett. 1995 Nov 6;97(2):145-8
references.pmid: 7497455
references.citation: Mol Cell Biol. 1996 Mar;16(3):1115-25
references.pmid: 8622656
references.citation: J Mol Med (Berl). 1996 Sep;74(9):505-13
references.pmid: 8892055
references.citation: Cancer Res. 1997 Feb 1;57(3):433-9
references.pmid: 9012470
references.citation: J Pathol. 1996 Dec;180(4):389-94
references.pmid: 9014859
references.citation: Cancer Res. 1997 Dec 15;57(24):5571-8
references.pmid: 9407969
references.citation: Int J Oncol. 1998 Feb;12(2):325-8
references.pmid: 9458357
references.citation: Laryngoscope. 1998 Sep;108(9):1413-7
references.pmid: 9738769
references.citation: Oncogene. 1999 Sep 9;18(36):5120-5
references.pmid: 10490849
references.citation: Cancer. 1999 Dec 1;86(11):2259-65
references.pmid: 10590366
references.citation: Am J Hum Genet. 2000 Jan;66(1):6-15
references.pmid: 10631132
references.citation: Digestion. 2000;61(4):237-46
references.pmid: 10878450
references.citation: Cancer Res. 2000 Oct 15;60(20):5767-72
references.pmid: 11059772
references.citation: CA Cancer J Clin. 2001 Jan-Feb;51(1):15-36
references.pmid: 11577478