Borbone, Eleonora (2009) EVALUATION OF HISTONE DEACETYLASE INHIBITOR EFFECTS ON THYROID CANCER. [Tesi di dottorato] (Unpublished)
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| Item Type: | Tesi di dottorato |
|---|---|
| Resource language: | English |
| Title: | EVALUATION OF HISTONE DEACETYLASE INHIBITOR EFFECTS ON THYROID CANCER |
| Creators: | Creators Email Borbone, Eleonora elly_norab@yahoo.it |
| Date: | 31 March 2009 |
| Number of Pages: | 89 |
| Institution: | Università degli Studi di Napoli Federico II |
| Istituzioni (extra): | CEINGE Biotecnologie Avanzate |
| 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: | 20 |
| Coordinatore del Corso di dottorato: | nome email Salvatore, Francesco UNSPECIFIED |
| Tutor: | nome email Fusco, Alfredo afusco@napoli.com Simeone, Antonio UNSPECIFIED Gronemeyer, Hinrich UNSPECIFIED |
| Date: | 31 March 2009 |
| Number of Pages: | 89 |
| Keywords: | HDAC, thyroid, cancer |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare Area 06 - Scienze mediche > MED/06 - Oncologia medica |
| Additional information: | Ciclo II/XX, Curriculum Molecular Oncology |
| Date Deposited: | 16 Nov 2009 14:59 |
| Last Modified: | 14 Jan 2015 12:26 |
| URI: | http://www.fedoa.unina.it/id/eprint/3402 |
| DOI: | 10.6092/UNINA/FEDOA/3402 |
Collection description
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.
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