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Gennaro Chiappetta,
Anna Basile,
Claudio Arra,
Daniela Califano,
Rosa Pasquinelli,
Antonio Barbieri, Veronica De Simone,
Domenica Rea,
Aldo Giudice,
Luciano Pezzullo,
Vincenzo De Laurenzi,
Gerardo Botti,
Simona Losito,
Daniela Conforti,
Maria Caterina Turco
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ABSTRACT: Anaplastic thyroid tumors (ATC) express high levels of BAG3, a member of the BAG family of cochaperone proteins that is involved in regulating cell apoptosis through multiple mechanisms.
The objective of the study was the investigation of the influence of B-cell lymphoma-2-associated athanogene 3 (BAG3) on ATC growth.
We investigated the effects of BAG3 down-modulation, obtained by using a specific small interfering RNA, on in vitro and in vivo growth of the human ATC cell line 8505C. Because BRAF protein plays an important role in ATC cell growth, we analyzed the effects of BAG3 down-modulation on BRAF protein levels. Furthermore, by using a proteasome inhibitor, we verified whether BAG3-mediated regulation of BRAF levels involved a proteasome-dependent mechanism.
BAG3 down-modulation significantly inhibits ATC growth in vitro and in vivo. BAG3 coimmunoprecipitates with BRAF protein, and its down-modulation results in a significant reduction of BRAF protein levels, which can be reverted by incubation with the proteasome inhibitor MG132.
BAG3 protein sustains ATC growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation. These results are in line with the reported ability of BAG3 to interfere with the proteasomal delivery of a number of other client proteins.
The Journal of clinical endocrinology and metabolism 11/2011; 97(1):E115-20. · 6.50 Impact Factor
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Daniela Califano,
Sandro Pignata,
Carmela Pisano,
Stefano Greggi,
Giuseppe Laurelli,
Nunzia Simona Losito,
Alessandro Ottaiano,
Adolfo Gallipoli,
Rosa Pasquinelli, Veronica De Simone,
Roberto Cirombella,
Alfredo Fusco,
Gennaro Chiappetta
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ABSTRACT: The FEZ1/LZTS1 (FEZ1) gene maps to chromosome 8p22 and is frequently altered in human cancer. FEZ1 has been proposed as a candidate tumour suppressor gene and its loss may contribute to tumour progression. We have analysed the expression of FEZ1 protein in tissues from ovarian carcinomas in relation to clinico-pathological variables, response to chemotherapy and disease-free and overall survival. FEZ1 status was assessed by immunohistochemistry. Cytoplasmic staining for FEZ1 protein was absent or drastically reduced in 38% of tumours. FEZ1 protein expression was not related to tumour grade, histotype, disease-free survival, or overall survival. On the contrary, it was significantly correlated with age and with FIGO stage of disease. This finding indicates that FEZ1 is involved in ovarian carcinogenesis. Moreover, loss of FEZ1 protein significantly predicted a complete treatment response in patients who received taxane-based chemotherapy. In conclusion, the reduction or loss of FEZ1 protein could be an aid to the clinical management of patients affected by ovarian carcinoma.
Journal of Cellular Physiology 11/2009; 222(2):382-6. · 3.87 Impact Factor
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Gennaro Chiappetta,
Angelo Ferraro,
Emilia Vuttariello,
Mario Monaco,
Francesca Galdiero, Veronica De Simone,
Daniela Califano,
Pierlorenzo Pallante,
Gerardo Botti,
Luciano Pezzullo,
Giovanna Maria Pierantoni,
Massimo Santoro,
Alfredo Fusco
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ABSTRACT: We have analysed the expression of the HMGA2 gene in a panel of normal and neoplastic thyroid tissues by immunohistochemistry and quantitative RT-PCR. HMGA2 protein was detectable in four out of 21 follicular carcinomas, 30 out of 45 papillary carcinomas, and 11 out of 12 undifferentiated carcinomas. As far as follicular thyroid adenomas are concerned, only three cases of the 31 analysed showed HMGA2 protein expression, whereas it was absent in seven normal thyroid tissues and in 12 hyperplastic nodules. Quantitative RT-PCR showed that almost all the papillary thyroid carcinomas and 13 out of 16 follicular thyroid carcinomas express much higher HMGA2 specific mRNA levels in comparison to normal thyroids and adenomas. Therefore, our data support the quantitative RT-PCR analysis of HMGA2 expression, rather than immunohistochemistry, as a powerful tool for the diagnosis of thyroid neoplasias.
European Journal of Cancer 06/2008; 44(7):1015-21. · 5.54 Impact Factor
