title: Microarray screening for target genes of the proto-oncogene PLAG1.
abstract: PLAG1 is a proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary glands and of lipoblastomas. As PLAG1 is a transcription factor, able to activate transcription through the binding to the consensus sequence GRGGC(N)(6-8)GGG, its ectopic expression presumably results in the deregulation of target genes, leading to uncontrolled cell proliferation. The identification of PLAG1 target genes is therefore a crucial step in understanding the molecular mechanisms involved in PLAG1-induced tumorigenesis. To this end, we analysed the changes in gene expression caused by the conditional induction of PLAG1 expression in fetal kidney 293 cell lines. Using oligonucleotide microarray analyses of about 12 000 genes, we consistently identified 47 genes induced and 12 genes repressed by PLAG1. One of the largest classes identified as upregulated PLAG1 targets consists of growth factors such as the insulin-like growth factor II and the cytokine-like factor 1. The in silico search for PLAG1 consensus sequences in the promoter of the upregulated genes reveals that a large proportion of them harbor several copies of the PLAG1-binding motif, suggesting that they represent direct PLAG1 targets. Our approach was complemented by the comparison of the expression profiles of pleomorphic adenomas induced by PLAG1 versus normal salivary glands. Concordance between these two sets of experiments pinpointed 12 genes that were significantly and consistently upregulated in pleomorphic adenomas and in PLAG1-expressing cells, identifying them as putative PLAG1 targets in these tumors.
authors.affiliation: Laboratory for Molecular Oncology, Center for Human Genetics, KU Leuven & Flanders Interuniversity Institute for Biotechnology, Herestraat 49, Leuven B-3000, Belgium. mvoz@ulg.ac.be
authors.forename: Marianne L
authors.initials: ML
authors.lastname: Voz
authors.forename: Janick
authors.initials: J
authors.lastname: Mathys
authors.forename: Karen
authors.initials: K
authors.lastname: Hensen
authors.forename: Hélène
authors.initials: H
authors.lastname: Pendeville
authors.forename: Isabelle
authors.initials: I
authors.lastname: Van Valckenborgh
authors.forename: Christophe
authors.initials: C
authors.lastname: Van Huffel
authors.forename: Marcela
authors.initials: M
authors.lastname: Chavez
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Van Damme
authors.forename: Bart
authors.initials: B
authors.lastname: De Moor
authors.forename: Yves
authors.initials: Y
authors.lastname: Moreau
authors.forename: Wim J M
authors.initials: WJ
authors.lastname: Van de Ven
mesh_terms: D000236:Adenoma / Q000235:genetics*; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012468:Salivary Gland Neoplasms / Q000235:genetics*; D012469:Salivary Glands / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; C104382:PLAG1 protein, human; D000090063:Proto-Oncogene Mas; D007335:Insulin-Like Growth Factor II