title: E1A-F is overexpressed early in human colorectal neoplasia and associated with cyclooxygenase-2 and matrix metalloproteinase-7.
abstract: Studies suggest the expression of cyclooxygenase-2 (COX-2) and matrilysin (MMP-7) increase in the early stages of colorectal carcinogenesis, however their interaction with other molecular markers is poorly understood. Results from cell line studies and mouse models suggest polyomavirus enhancer activator 3 (PEA3) may play a role in the activation of COX-2 and MMP-7 promoters. However, the role of E1A-F, the human homolog of murine PEA3, in colorectal cancer (CRC) development has not been elucidated. In this study, we used real-time reverse transcription (RT)-polymerase chain reaction (PCR) to measure the levels of E1A-F, COX-2, and MMP-7 in matched normal mucosa, adenomas, and/or carcinomas from 128 patients. Our results demonstrate significant overexpression of E1A-F and MMP-7 in adenomas and E1A-F, COX-2, and MMP-7 in carcinomas. In carcinomas, E1A-F expression was significantly associated with both COX-2 and MMP-7 overexpression. These results suggest E1A-F is overexpressed in early stages of human CRC development and may be an important factor in the overexpression of COX-2 and MMP-7.
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, 35243, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Boedefeld
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
authors.forename: Heidi
authors.initials: H
authors.lastname: Weiss
authors.forename: Robert B
authors.initials: RB
authors.lastname: Diasio
authors.forename: Marshall M
authors.initials: MM
authors.lastname: Urist
authors.forename: Kirby I
authors.initials: KI
authors.lastname: Bland
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Heslin
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism*; D051546:Cyclooxygenase 2; D017931:DNA Primers; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017500:Adenovirus E1A Proteins; D017931:DNA Primers; C079853:ETV4 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D020783:Matrix Metalloproteinase 7