Ferraro, Angelo (2011) Biological function of Cl 2 gene and it’s role in thyroid cancer. [Tesi di dottorato] (Unpublished)


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Item Type: Tesi di dottorato
Lingua: English
Title: Biological function of Cl 2 gene and it’s role in thyroid cancer
Ferraro, Angeloferraro@ceinge.unina.it
Date: 2011
Number of Pages: 61
Institution: Università degli Studi di Napoli Federico II
Istituzioni (extra): CEINGE  Biotecnologie Avanzate, TIGEM – Telethon Insitute of Genetics and Medicine
Department: CEINGE Biotecnologie avanzate
Scuola di dottorato: SEMM – European School of Molecular Medicine
Dottorato: PhD in Molecular Medicine (Molecular Oncology or Human Genetics)
Ciclo di dottorato: 21
Coordinatore del Corso di dottorato:
Salvatore, Francescosalvator@unina.it
Fusco, Alfredoalfusco@napoli.com
Russo, Tommasotommaso.russo@unina.it
Date: 2011
Number of Pages: 61
Uncontrolled Keywords: Thyroid cancer,tumor suppressor
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Area 06 - Scienze mediche > MED/04 - Patologia generale
Additional Information: Ciclo III/XXI, Curriculum: Molecular Oncology
Date Deposited: 05 Feb 2010 16:17
Last Modified: 14 Jan 2015 11:39
URI: http://www.fedoa.unina.it/id/eprint/4315
DOI: 10.6092/UNINA/FEDOA/4315


Here I report data to support a tumor suppressor role of the Cl 2 gene. Indeed, I detected a drastic reduction, of Cl 2 gene expression in almost all thyroid carcinomas analyzed, with respect to normal thyroid, with the lowest expression levels observed in the follicular variants of papillary carcinomas. Loss of heterozygosity and CpG hypermethylation at the second exon likely accounts for Cl 2 downregulation in thyroid carcinomas. A drastic reduction in Cl 2 expression, with respect to normal counterpart tissues, was also observed in breast, colon and ovarian carcinomas. The restoration of Cl 2 expression in two human thyroid anaplastic carcinoma cell lines leads to the suppression of the malignant phenotype associated with a higher susceptibility to apoptosis. The development of thyroid adenomas and ovarian carcinomas in Cl knock-out mice validates the tumor suppressor role of Cl 2 gene. Finally, transgenic mice for RET/PTC1 oncogene crossed with the Cl 2 knock-out mice developed much more aggressive thyroid carcinomas compared with those observed in the single mutant RET/PTC 1 mice. Therefore, these results taken together indicate Cl 2 as a putative tumor suppressor gene in the process of human thyroid carcinogenesis.


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