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Article

Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene

by
Mario Monaco
1,†,
Giuseppe Palma
2,†,
Michela Vitiello
3,
Anna Capiluongo
1,
Barbara D’Andrea
4,
Emilia Vuttariello
1,
Antonio Luciano
2,
Laura Cerchia
3,
Gennaro Chiappetta
1,
Claudio Arra
2,
Alfredo Fusco
5 and
Monica Fedele
3,*
1
Dipartimento di Ricerca Traslazionale a Supporto dei Percorsi Oncologici, S.C. Genomica Funzionale, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, 80131 Naples, Italy
2
S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori—IRCCS—Fondazione G. Pascale, 80131 Naples, Italy
3
CNR—Institute of Experimental Endocrinology and Oncology (IEOS), 80131 Naples, Italy
4
Centro Medico Polispecialistico (CMO), 80100 Naples, Italy
5
Department of Molecular Medicine and Medical Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2018, 10(4), 92; https://doi.org/10.3390/cancers10040092
Submission received: 14 February 2018 / Revised: 21 March 2018 / Accepted: 21 March 2018 / Published: 27 March 2018
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Abstract

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is an emerging cancer-related gene that is downregulated in different human malignancies, including thyroid cancer, where its levels gradually decrease going from papillary thyroid carcinomas (PTC) to poorly differentiated and undifferentiated highly aggressive anaplastic carcinomas (ATC). The restoration of PATZ1 expression in thyroid cancer cells reverted their malignant phenotype by inducing mesenchymal-to-epithelial transition, thus validating a tumor suppressor role for PATZ1 and suggesting its involvement in thyroid cancer progression. Here, we investigated the consequences of the homozygous and heterozygous loss of PATZ1 in the context of a mouse modeling of PTC, represented by mice carrying the RET/PTC1 oncogene under the thyroid specific control of the thyroglobulin promoter RET/PTC1 (RET/PTC1TG). The phenotypic analysis of RET/PTC1TG mice intercrossed with Patz1-knockout mice revealed that deficiency of both Patz1 alleles enhanced thyroid cancer incidence in RET/PTC1TG mice, but not the heterozygous knockout of the Patz1 gene. However, both RET/PTC1TG;Patz1+/− and RET/PTC1TG;Patz1−/− mice developed a more aggressive thyroid cancer phenotype—characterized by higher Ki-67 expression, presence of ATCs, and increased incidence of solid variants of PTC—than that shown by RET/PTC1TG; Patz1+/+ compound mice. These results confirm that PATZ1 downregulation has a critical role in thyroid carcinogenesis, showing that it cooperates with RET/PTC1 in thyroid cancer progression.
Keywords: thyroid cancer; PATZ1; RET/PTC; mice; solid variant; anaplastic thyroid cancer; PATZ1; RET/PTC; mice; solid variant; anaplastic

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MDPI and ACS Style

Monaco, M.; Palma, G.; Vitiello, M.; Capiluongo, A.; D’Andrea, B.; Vuttariello, E.; Luciano, A.; Cerchia, L.; Chiappetta, G.; Arra, C.; et al. Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene. Cancers 2018, 10, 92. https://doi.org/10.3390/cancers10040092

AMA Style

Monaco M, Palma G, Vitiello M, Capiluongo A, D’Andrea B, Vuttariello E, Luciano A, Cerchia L, Chiappetta G, Arra C, et al. Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene. Cancers. 2018; 10(4):92. https://doi.org/10.3390/cancers10040092

Chicago/Turabian Style

Monaco, Mario, Giuseppe Palma, Michela Vitiello, Anna Capiluongo, Barbara D’Andrea, Emilia Vuttariello, Antonio Luciano, Laura Cerchia, Gennaro Chiappetta, Claudio Arra, and et al. 2018. "Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene" Cancers 10, no. 4: 92. https://doi.org/10.3390/cancers10040092

APA Style

Monaco, M., Palma, G., Vitiello, M., Capiluongo, A., D’Andrea, B., Vuttariello, E., Luciano, A., Cerchia, L., Chiappetta, G., Arra, C., Fusco, A., & Fedele, M. (2018). Loss of One or Two PATZ1 Alleles Has a Critical Role in the Progression of Thyroid Carcinomas Induced by the RET/PTC1 Oncogene. Cancers, 10(4), 92. https://doi.org/10.3390/cancers10040092

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