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Human Papilloma Virus 16 E7 Oncogene Does Not Cooperate With RET/PTC 3 Oncogene in the Neoplastic Transformation of Thyroid Cells in Transgenic Mice

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We have previously reported that the thyroid-targeted expression of the RET/PTC3 oncogene (Tg-RET/PTC3) in transgenic mice induces follicular hyperplasia with papillary architecture, resulting in a modest increase of the thyroid gland volume, followed by the appearance of papillary carcinomas in approximately 1-year-old animals. In order to analyze the genetic alterations that may cooperate with RET/PTC3 in the development or progression of thyroid tumors, we interbred Tg-RET/PTC3 mice with Tg-E7 transgenic mice, which express the E7 oncogene of the human papilloma virus 16 in thyroid cells. Tg-E7 mice develop large colloid goiters with small papillae and well-differentiated thyroid carcinomas in older animals. Here we show that thyroid lesions in Tg-RET/PTC3-Tg-E7 double transgenics were morphologically different from those occurring in Tg-RET/PTC3 mice, while they were virtually indistinguishable from those occurring in Tg-E7 mice. In addition, the coexpression of RET/PTC3 and E7 oncogenes neither enhanced the malignant phenotype nor reduced the latency period of thyroid lesions with respect to parental transgenic lines. We conclude that the coexpression of RET/PTC3 and E7 lacks any cooperative effect in the neoplastic transformation of thyroid cells and that the E7-induced thyroid phenotype is dominant with respect to the RET/PTC3 one.

Keywords: E7 oncogene; Goiter; Key words: Thyroid; Neoplasia; RET/PTC3 oncogene; Tumorigenesis

Document Type: Research Article


Affiliations: 1: *Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, e Funzionali-Istituto di Anatomia Patologica, Università “Federico II,” 80131 Naples, Italy 2: †Dipartimento di Scienze Biomorfologiche e Funzionali-Istituto di Anatomia Patologica, Università “Federico II,” 80131 Naples, Italy 3: ‡University of Brussels, School of Medicine, Institute of Interdisciplinary Research (IRIBHN), B 1070 Brussels, Belgium 4: §Department of Otolaryngology-HNS, Thomas Jefferson University, Kimmel Cancer Institute, Jefferson Medical College, Philadelphia, PA 5: ¶Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia, Università “Magna Graecia,” 88100 Catanzaro, Italy

Publication date: 2001-08-01

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