Human papilloma virus 16 E7 oncogene does not cooperate with RET/PTC 3 oncogene in the neoplastic transformation of thyroid cells in transgenic mice

We have previously reported that the thyroid-targeted expression of the RET /PTC3 oncogene (Tg-RET/PTC3) in transgenic mice induces follicular hyperpla sia with papillary architecture, resulting in a modest increase of the thyr oid gland volume, followed by the appearance of papillary carcinomas in app roximately 1-year-old animals. In order to analyze the genetic alterations that may cooperate with RET/PTC3 in the development or progression of thyro id 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. T g-E7 mice develop large colloid goiters with small papillae and well-differ entiated thyroid carcinomas in older animals. Here we show that thyroid les ions in Tg-RET/PTC3-Tg-E7 double transgenics were morphologically different from those occurring in Tg-RET/PTC3 mice, while they were virtually indist inguishable from those occurring in Tg-E7 mice. In addition, the coexpressi on of RET/PTC3 and E7 oncogenes neither enhanced the malignant phenotype no r reduced the latency period of thyroid lesions with respect to parental tr ansgenic lines. We conclude that the coexpression of RET/PTC3 and E7 lacks any cooperative effect in the neoplastic transformation of thyroid cells an d that the E7-induced thyroid phenotype is dominant with respect to the RET /PTC3 one.