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Title: Upregulation of Igf and Wnt signalling associated genes in pleomorphic adenomas of the salivary glands in PLAG1 transgenic mice
Authors: Declercq, Jeroen ×
Van Dyck, Frederik
Van Damme, Boudewijn
Van de Ven, Willem #
Issue Date: May-2008
Publisher: Lychnia
Series Title: International Journal of Oncology vol:32 issue:5 pages:1041-1047
Abstract: The Pleomorphic adenoma gene 1 (PLAG1) is involved in various human neoplasias, including pleomorphic adenomas of the salivary glands. Moreover, the oncogenic role of PLAG1 was clearly demonstrated in two independent PLAG1 transgenic mouse founders, in which PLAG1 expression could be targeted to different tissues using the Cre/loxP system. MMTV-Cre-mediated targeted overexpression of PLAG1 in the salivary glands of double transgenic offspring mice, referred to as P1-MCre and P2-MCre mice, induced pleomorphic adenomas in this organ. Igf2, a genuine PLAG1 target gene, was highly upregulated in those tumours as well as in human pleomorphic adenomas of the salivary glands. These and previous observations in other PLAG1-induced tumours e.g. breast adenomyoepitheliomas emphasize the importance of Igf upregulation in such tumours. In this study, further evidence for the role of Igf2 in PLAG1-induced tumourigenesis, is reported. Inactivation of Igf2 in P1-MCre mice leads to a significant delay in tumour development. Since tumour development is not fully abrogated by inactivation of Igf2, other signalling pathways are likely to contribute to PLAG1-induced tumourigenesis as well. Further studies revealed that several genes such as H19, Dlk1, Gtl2, Igfbp2, Igfbp3 and genes involved in Wnt signalling, such as Wnt6, Cyclin D1 and beta-catenin are upregulated in P1-MCre mice in which Igf2 is inactivated. In conclusion, we clearly demonstrate upregulation of several genes associated with Igf and Wnt signalling in PLAG1-induced pleomorphic adenomas. Furthermore, inactivation of Igf2 does not affect upregulation of genes associated with Wnt signalling, which might suggest that both signalling pathways are involved.
URI: 
ISSN: 1019-6439
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdepartemental Stem Cell Institute (-)
Translational Cell & Tissue Research
Department of Human Genetics - miscellaneous
Laboratory for Biochemical Neuroendocrinology
× corresponding author
# (joint) last author

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