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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

DOI: http://dx.doi.org/10.3727/096504001108747800

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: January 1, 2001

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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