Survivin is Highly Expressed and Promotes Cell Survival in Malignant Peritoneal Mesothelioma

Background: The biology of malignant peritoneal mesothelioma (MPM) is largely unknown. In the present study, we assessed the expression of survivin and other members of the inhibitors of apoptosis proteins (IAP) family (IAP-1, IAP-2 and X-IAP) in a series of 32 MPM surgical specimens and investigate...

Full description

Saved in:
Bibliographic Details
Main Authors: Nadia Zaffaroni, Aurora Costa, Marzia Pennati, Cinzia De Marco, Emanuela Affini, Maria Madeo, Roberta Erdas, Antonello Cabras, Shigeki Kusamura, Dario Baratti, Marcello Deraco, Maria Grazia Daidone
Format: Article
Language:English
Published: Wiley 2007-01-01
Series:Cellular Oncology
Online Access:http://dx.doi.org/10.1155/2007/456839
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832556341782118400
author Nadia Zaffaroni
Aurora Costa
Marzia Pennati
Cinzia De Marco
Emanuela Affini
Maria Madeo
Roberta Erdas
Antonello Cabras
Shigeki Kusamura
Dario Baratti
Marcello Deraco
Maria Grazia Daidone
author_facet Nadia Zaffaroni
Aurora Costa
Marzia Pennati
Cinzia De Marco
Emanuela Affini
Maria Madeo
Roberta Erdas
Antonello Cabras
Shigeki Kusamura
Dario Baratti
Marcello Deraco
Maria Grazia Daidone
author_sort Nadia Zaffaroni
collection DOAJ
description Background: The biology of malignant peritoneal mesothelioma (MPM) is largely unknown. In the present study, we assessed the expression of survivin and other members of the inhibitors of apoptosis proteins (IAP) family (IAP-1, IAP-2 and X-IAP) in a series of 32 MPM surgical specimens and investigated the effects of survivin knockdown in an established MPM cell line. Methods: Expression of different IAPs was measured by immunohistochemistry. MPM cells were transfected with a small-interfering RNA (siRNA) targeting survivin mRNA and analyzed for survivin expression, growth rate, and ability to undergo spontaneous and drug (cisplatin, doxorubicin)-induced apoptosis. Results: Survivin expression was observed in 29 (91%) surgical MPM specimens, whereas the positivity rate for the other IAPs ranged from 69% to 100%. Transfection of MPM cells with the survivin siRNA induced a marked inhibition of survivin protein expression, a time-dependent decline in cell growth and an enhanced rate of spontaneous and drug-induced apoptosis, with a concomitant increase in the catalytic activity of caspase-9. Conclusion: Our results show for the first time that survivin, as well as other IAPs, is largely expressed in clinical MPMs and suggest that strategies aimed at down-regulating survivin may provide a novel approach for the treatment of the malignancy.
format Article
id doaj-art-7669552b1d7e4a39b3839485f0181bf4
institution Kabale University
issn 1570-5870
1875-8606
language English
publishDate 2007-01-01
publisher Wiley
record_format Article
series Cellular Oncology
spelling doaj-art-7669552b1d7e4a39b3839485f0181bf42025-02-03T05:45:38ZengWileyCellular Oncology1570-58701875-86062007-01-0129645346610.1155/2007/456839Survivin is Highly Expressed and Promotes Cell Survival in Malignant Peritoneal MesotheliomaNadia Zaffaroni0Aurora Costa1Marzia Pennati2Cinzia De Marco3Emanuela Affini4Maria Madeo5Roberta Erdas6Antonello Cabras7Shigeki Kusamura8Dario Baratti9Marcello Deraco10Maria Grazia Daidone11Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyBackground: The biology of malignant peritoneal mesothelioma (MPM) is largely unknown. In the present study, we assessed the expression of survivin and other members of the inhibitors of apoptosis proteins (IAP) family (IAP-1, IAP-2 and X-IAP) in a series of 32 MPM surgical specimens and investigated the effects of survivin knockdown in an established MPM cell line. Methods: Expression of different IAPs was measured by immunohistochemistry. MPM cells were transfected with a small-interfering RNA (siRNA) targeting survivin mRNA and analyzed for survivin expression, growth rate, and ability to undergo spontaneous and drug (cisplatin, doxorubicin)-induced apoptosis. Results: Survivin expression was observed in 29 (91%) surgical MPM specimens, whereas the positivity rate for the other IAPs ranged from 69% to 100%. Transfection of MPM cells with the survivin siRNA induced a marked inhibition of survivin protein expression, a time-dependent decline in cell growth and an enhanced rate of spontaneous and drug-induced apoptosis, with a concomitant increase in the catalytic activity of caspase-9. Conclusion: Our results show for the first time that survivin, as well as other IAPs, is largely expressed in clinical MPMs and suggest that strategies aimed at down-regulating survivin may provide a novel approach for the treatment of the malignancy.http://dx.doi.org/10.1155/2007/456839
spellingShingle Nadia Zaffaroni
Aurora Costa
Marzia Pennati
Cinzia De Marco
Emanuela Affini
Maria Madeo
Roberta Erdas
Antonello Cabras
Shigeki Kusamura
Dario Baratti
Marcello Deraco
Maria Grazia Daidone
Survivin is Highly Expressed and Promotes Cell Survival in Malignant Peritoneal Mesothelioma
Cellular Oncology
title Survivin is Highly Expressed and Promotes Cell Survival in Malignant Peritoneal Mesothelioma
title_full Survivin is Highly Expressed and Promotes Cell Survival in Malignant Peritoneal Mesothelioma
title_fullStr Survivin is Highly Expressed and Promotes Cell Survival in Malignant Peritoneal Mesothelioma
title_full_unstemmed Survivin is Highly Expressed and Promotes Cell Survival in Malignant Peritoneal Mesothelioma
title_short Survivin is Highly Expressed and Promotes Cell Survival in Malignant Peritoneal Mesothelioma
title_sort survivin is highly expressed and promotes cell survival in malignant peritoneal mesothelioma
url http://dx.doi.org/10.1155/2007/456839
work_keys_str_mv AT nadiazaffaroni survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT auroracosta survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT marziapennati survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT cinziademarco survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT emanuelaaffini survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT mariamadeo survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT robertaerdas survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT antonellocabras survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT shigekikusamura survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT dariobaratti survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT marcelloderaco survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma
AT mariagraziadaidone survivinishighlyexpressedandpromotescellsurvivalinmalignantperitonealmesothelioma