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 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.


CONCLUSIONS
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.
Zaffaroni
Nadia
N
Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. zaffaroni@istitutotumori.mi.it
Costa
Aurora
A
Pennati
Marzia
M
De Marco
Cinzia
C
Affini
Emanuela
E
Madeo
Maria
M
Erdas
Roberta
R
Cabras
Antonello
A
Kusamura
Shigeki
S
Baratti
Dario
D
Deraco
Marcello
M
Daidone
Maria Grazia
MG
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000502:physiology; D008297:Male; D008654:Mesothelioma / Q000737:chemistry / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000502:physiology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology*; D010534:Peritoneal Neoplasms / Q000737:chemistry / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D053453:Caspase 9