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   <subfield code="a">The PTC oncogene is able to dedifferentiate a rat thyroid epithelial cell line in culture</subfield>
   <subfield code="h">[Elektronische Daten]</subfield>
   <subfield code="c">[Massimo Santoro, Rosamarina Melillo, Michele Grieco, Aniello Cerrato, Alfredo Fusco, Giancarlo Vecchio, Corrisp Salvatore]</subfield>
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   <subfield code="a">We have recently cloned a new oncogene from human papillary thyroid carcinomas, which we have designatedPTC. This oncogene consists of a chimeric gene, the 5′-end of which corresponds to a gene of unknown function, designated H4, while the 3′ portion corresponds to the tyrosine kinase domain of theRET proto-oncogene. We constructed a retroviral vector containing thePTC oncogene under the transcriptional control of the Moloney LTR, and then produced the corresponding defective retrovirus by transfecting the retroviral vector onto Psi-2 cells. We subsequently used this retrovirus to infect a differentiated rat thyroid cell line (PC-C1-3) which is dependent on TSH for growth. Upon infection with thePTC virus the PC-C1-3 cells no longer depended on TSH for growth. Furthermore, the infected cells lost completely their differentiated functions,i.e. thyroglobulin and TSH-receptor genes expression and iodide uptake. However, they retained their non malignant phenotype in that they were not able to grow in semisolid media nor in the athymic mice. The introduction in the PC-C1-3 cell line of both thePTC and the activated viral Ha-ras oncogenes resulted in the appearance of a completely undifferentiated and malignant phenotype. These results demonstrate that:a) ThePTC oncogene, which plays an important role in human thyroid carcinogenesis, is also able to induce the complete dedifferentiation of rat thyroid cellsin vitro;b) Two cytoplasmic oncogenes (Ha-ras andPTC) cooperate in the induction of a fully malignant phenotype of a thyroid differentiated cell line.</subfield>
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   <subfield code="a">Accademia nazionale dei Lincei, 1992</subfield>
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   <subfield code="a">Thyroid</subfield>
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   <subfield code="u">Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R. Dipartimento di Biologia e Patologia Cellulare e Molecolare «L. Califano» II Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli «Federico II», Via S. Pansini, 5-80131, Napoli</subfield>
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   <subfield code="u">Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R. Dipartimento di Biologia e Patologia Cellulare e Molecolare «L. Califano» II Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli «Federico II», Via S. Pansini, 5-80131, Napoli</subfield>
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   <subfield code="u">Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R. Dipartimento di Biologia e Patologia Cellulare e Molecolare «L. Califano» II Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli «Federico II», Via S. Pansini, 5-80131, Napoli</subfield>
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   <subfield code="u">Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R. Dipartimento di Biologia e Patologia Cellulare e Molecolare «L. Califano» II Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli «Federico II», Via S. Pansini, 5-80131, Napoli</subfield>
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   <subfield code="g">3/3(1992-09-01), 257-267</subfield>
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