title: Lap2alpha expression is controlled by E2F and deregulated in various human tumors.
abstract: Deregulation of the retinoblastoma (pRB) tumor suppressor pathway is frequently observed in human cancer and associated with aberrant activity of E2F transcription factors. We have performed microarray based analysis with the aim of identifying potential downstream mediators of the tumor suppressing activity of pRB. Here we report that the expression of LAP2 (lamina-associated polypeptide 2) is under direct control of E2F transcription factors. Chromatin immunoprecipitation assays show that the LAP2 promoter is bound by endogenous E2F in vivo. The LAP2 promoter is transactivated by ectopically expressed E2F and mutation of E2F binding sites eliminates this effect. We studied the expression level of LAP2alpha in human tumors by tissue microarray analysis and found LAP2alpha over expression in a significant percentage of primary larynx, lung, stomach, breast, and colon cancer tissues. In agreement with its regulation by E2F, LAP2alpha over expression in primary tumors was found to be correlated with tumor proliferation rate.
authors.affiliation: The FIRC Institute of Molecular Oncology Foundation, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Parise
authors.forename: Giacomo
authors.initials: G
authors.lastname: Finocchiaro
authors.forename: Barabara
authors.initials: B
authors.lastname: Masciadri
authors.forename: Micaela
authors.initials: M
authors.lastname: Quarto
authors.forename: Stefanie
authors.initials: S
authors.lastname: Francois
authors.forename: Francesco
authors.initials: F
authors.lastname: Mancuso
authors.forename: Heiko
authors.initials: H
authors.lastname: Muller
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D050684:E2F Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007438:Introns / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D008565:Membrane Proteins; C093413:lamina-associated polypeptide 2