EVALUATION OF HISTONE DEACETYLASE INHIBITOR EFFECTS ON THYROID CANCER

BORBONE, ELEONORA (2009) EVALUATION OF HISTONE DEACETYLASE INHIBITOR EFFECTS ON THYROID CANCER. [Tesi di dottorato] (Inedito)

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Abstract

Abstract Histone deacetylases (HDACs) play a crucial role in the proper regulation of cellular functions through their connection with chromatin and transcriptional regulation. Alterations in HDAC activity have been reported in several types of cancer encouraging development of HDAC inhibitors (HDACis) for cancer treatment. The antitumor activity of HDACi has been demonstrated, in clinical trials, in both solid and non solid neoplasias at doses well tolerated by patients. However, the molecular basis for their tumor selectivity is unknown. Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies, having a poor prognosis and being refractory to conventional chemo- and radiotherapy. To the aim to find an innovative therapy for the treatment of ATCs, we studied the effects of two potent HDACis, SAHA and MS-275, on rat thyroid cell lines transformed by the v-ras-Ki oncogene which is frequently mutated in ATCs. We show that: i) HDAC 1 and HDAC 2 are overexpressed in anaplastic thyroid carcinomas compared to normal thyroid; ii) SAHA and MS-275 induce apoptosis selectively in completely transformed rat thyroid cells; iii) TNF-related apoptosis-inducing ligand (TRAIL) is the main mediator of cell death induced by SAHA; iv) SAHA stabilize TRAIL protein by affecting its proteasome-mediated degradation.

Tipologia di documento:Tesi di dottorato
Parole chiave:HDAC, thyroid, cancer
Settori scientifico-disciplinari MIUR:Area 05 Scienze biologiche > BIO/11 BIOLOGIA MOLECOLARE
Area 06 Scienze mediche > MED/06 ONCOLOGIA MEDICA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Salvatore, Francesco
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
Fusco, Alfredoafusco@napoli.com
Simeone, Antonio
Gronemeyer, Hinrich
Stato del full text:Accessibile
Data:31 Marzo 2009
Numero di pagine:89
Istituzione:Università degli studi di Napoli Federico II
Dipartimento o Struttura:CEINGE Biotecnologie Avanzate
Tipo di tesi:Dottorato
Stato dell'Eprint:Inedito
Scuola di dottorato:SCUOLA EUROPEA DI MEDICINA MOLECOLARE - SEMM sede di Napoli
Denominazione del dottorato:PhD in MOLECULAR MEDICINE, curriculum Molecular Oncology
Ciclo di dottorato:XX
Numero di sistema:3402
Depositato il:16 Novembre 2009 15:59
Ultima modifica:09 Settembre 2010 11:55

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