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 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.
Portella
G
G
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università Federico II, Naples, Italy. Portella@cds.unina.it
Borselli
C
C
Santoro
M
M
Gerbasio
D
D
D'Armiento
M R
MR
Dumont
J E
JE
Ledent
C
C
Rothstein
J L
JL
Vecchio
G
G
Fusco
A
A
D000367:Age Factors; D000818:Animals; D002291:Carcinoma, Papillary / Q000209:etiology* / Q000473:pathology / Q000821:virology; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D005260:Female; D006042:Goiter / Q000209:etiology / Q000473:pathology / Q000821:virology; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000494:pharmacology*; D050725:Papillomavirus E7 Proteins; D010641:Phenotype; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000473:pathology / Q000821:virology; D013997:Time Factors; D014157:Transcription Factors
C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D014157:Transcription Factors; C059731:oncogene protein E7, Human papillomavirus type 16