Gene expression in RET/PTC3 and E7 transgenic mouse thyroids: RET/PTC3 but not E7 tumors are partial
June 29th, 2008 | by admin |Gene expression in RET/PTC3 and E7 transgenic mouse thyroids: RET/PTC3 but not E7 tumors are partial and transient models of human papillary thyroid cancers.
We studied gene expression profiles in two mouse models of human thyroid carcinoma: the Tg-RET/PTC3 (RP3) and Tg-E7 mice. RP3 fusion gene is the most frequent mutation found in the first wave post-Chernobyl papillary thyroid cancers (PTC). E7 is an oncoprotein derived from the Human Papillomavirus 16 (HPV16) responsible for most cervical carcinoma in women. Both transgenic mice develop thyroid hyperplasia followed by solid differentiated carcinoma in older animals. To understand the different steps leading to carcinoma, we analyzed thyroid gene expression in both strains at different ages by microarray technology. Important biological processes were differentially regulated in the two tumor types. In E7 thyroids cell cycle was the most upregulated process, an observation consistent with the huge size of these tumors. In RP3 thyroids, contrary to E7 tumors, several human PTC characteristics were observed: overexpression of many immune-related genes, regulation of human PTC markers, upregulation of EGF-like growth factors and significant regulation of angiogenesis and extracellular matrix remodeling-related genes. However similarities were incomplete; they did not concern the overall gene expression and were not conserved in old animals. Therefore RP3 tumors are partial and transient models of human PTC. They constitute a good model, especially in young animals, to study the respective role of the biological processes shared with human PTC and will allow testing drugs targeting these validated variables.
Burniat A, Jin L, Detours V, Driessens N, Goffard JC, Santoro M, Rothstein J, Dumont JE, Miot F, Corvilain B.
Institute of Interdisciplinary Research, School of Medecine, Université libre de Bruxelles, Campus Erasme, Brussels, Belgium; Istituto di Endocrinologia ed Oncologia Sperimentale del CNR « G.Salvatore », c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita\’ Federico II, Naples, Italy; Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA; Amgen, Inc. Inflammation Research 1201 Amgen Ct. West Seattle, WA 98103; Department of Endocrinology, Erasme University Hospital, Université Libre de Bruxelles, Campus Erasme, Brussels, Belgium.