This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Declercq, J. Articles by Van de Ven, W. J.M. Search for Related Content PubMed PubMed Citation Articles by Declercq, J. Articles by Van de Ven, W. J.M.

Salivary Gland Tumors in Transgenic Mice with Targeted PLAG1 Proto-Oncogene Overexpression

¹ Laboratory for Molecular Oncology, Department of Human Genetics, K.U. Leuven and Flanders Interuniversity Institute for Biotechnology; ² Thromb-X, n.v., Campus Gasthuisberg; ³ Department of Morphology and Molecular Pathology, K.U. Leuven, Leuven, Belgium; ⁴ Service Central de Cytologie and Anatomie pathologique, Hôpital Lariboisière; and ⁵ Unité de Recherche et d'Expertise en Histotechnologie et Pathologie, Institut Pasteur, Paris, France

Requests for reprints: Wim J.M. van de Ven, Laboratory for Molecular Oncology, Department of Human Genetics, K.U. Leuven, Herestraat 49, B-3000 Leuven, Belgium. Phone: 32-16-345987; Fax: 32-16-346073; E-mail: wim.vandeven{at}med.kuleuven.ac.be.

Pleomorphic adenoma gene 1 (PLAG1) proto-oncogene overexpression is implicated in various human neoplasias, including salivary gland pleomorphic adenomas. To further assess the oncogenic capacity of PLAG1, two independent PLAG1 transgenic mouse strains were established, PTMS1 and PTMS2, in which activation of PLAG1 overexpression is Cre mediated. Crossbreeding of PTMS1 or PTMS2 mice with MMTV-Cre transgenic mice was done to target PLAG1 overexpression to salivary and mammary glands, in the P1-Mcre/P2-Mcre offspring. With a prevalence of 100% and 6%, respectively, P1-Mcre and P2-Mcre mice developed salivary gland tumors displaying various pleomorphic adenoma features. Moreover, histopathologic analysis of salivary glands of 1-week-old P1-Mcre mice pointed at early tumoral stages in epithelial structures. Malignant characteristics in the salivary gland tumors and frequent lung metastases were found in older tumor-bearing mice. PLAG1 overexpression was shown in all tumors, including early tumoral stages. The tumors revealed an up-regulation of the expression of two distinct, imprinted gene clusters (i.e., Igf2/H19 and Dlk1/Gtl2). With a latency period of about 1 year, 8% of the P2-Mcre mice developed mammary gland tumors displaying similar histopathologic features as the salivary gland tumors. In conclusion, our results establish the strong and apparently direct in vivo tumorigenic capacity of PLAG1 and indicate that the transgenic mice constitute a valuable model for pleomorphic salivary gland tumorigenesis and potentially for other glands as well.

This article has been cited by other articles:

				L. Queimado, D. Obeso, M. D. Hatfield, Y. Yang, D. M. Thompson, and A. M.C. Reis Dysregulation of Wnt Pathway Components in Human Salivary Gland Tumors Arch Otolaryngol Head Neck Surg, January 1, 2008; 134(1): 94 - 101. [Abstract] [Full Text] [PDF]

				I. Cleynen, C. Huysmans, T. Sasazuki, S. Shirasawa, W. Van de Ven, and K. Peeters Transcriptional Control of the Human High Mobility Group A1 Gene: Basal and Oncogenic Ras-Regulated Expression Cancer Res., May 15, 2007; 67(10): 4620 - 4629. [Abstract] [Full Text] [PDF]