[en] 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.
Research center :
Giga-Development and Stem Cells - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Voz, Marianne ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Mathys, Janick; Katholieke Universiteit Leuven - KUL > ESAT-SCD
Hensen, Karen; Katholieke Universiteit Leuven - KUL > Center for Human Genetics > Laboratory for Molecular Oncology
Pendeville, Helene; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Van Valckenborgh, Isabelle; Katholieke Universiteit Leuven - KUL > Center for Human Genetics > Laboratory for Molecular Oncology
Van Huffel, Christophe; Starlab > Department of Genomics
Chavez, Marcela; Katholieke Universiteit Leuven - KUL > Center for Human Genetics > Laboratory for Molecular Oncology
Van Damme, Boudewijn; Katholieke Universiteit Leuven - KUL > Department of Morphology and Molecular Pathology
De Moor, Bart; Katholieke Universiteit Leuven - KUL > ESAT-SCD
Moreau, Yves; Université de Liège - ULiège > Laboratoire de Biologie Mole´culaire et de Ge´nie Ge´ne´tique
Van de Ven, Wim J M; Katholieke Universiteit Leuven - KUL > Center for Human Genetics > Laboratory for Molecular Oncology
Language :
English
Title :
Microarray screening for target genes of the proto-oncogene PLAG1.
Publication date :
2004
Journal title :
Oncogene
ISSN :
0950-9232
eISSN :
1476-5594
Publisher :
Nature Publishing Group, Basingstoke, United Kingdom
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