Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas

Second mitochondria‐derived activator of caspases (Smac/DIABLO) is released from mitochondria into the cytosol during apoptosis, promoting caspase activation by neutralizing the inhibition of inhibitor of apoptosis proteins (IAPs) on caspases. Alteration of apoptosis is essential for cancer developm...

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Published in:APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2003-03, Vol.111 (3), p.382-388
Main Authors: YOO, NAM JIN, KIM, HONG SUG, KIM, SU YOUNG, PARK, WON SANG, PARK, CHO HYUN, JEON, HAE MYUNG, JUNG, EUN SUN, LEE, JUNG YOUNG, LEE, SUG HYUNG
Format: Article
Language:English
Subjects:
apoptosis
Apoptosis - physiology
Biological and medical sciences
carcinoma
Carcinoma - metabolism
Carcinoma - pathology
Carrier Proteins - biosynthesis
DIABLO
Host-tumor relations. Immunology. Biological markers
Humans
Immunohistochemistry
Intracellular Signaling Peptides and Proteins
Male
Medical sciences
Mitochondrial Proteins - biosynthesis
Neoplasms - metabolism
Neoplasms - pathology
sarcoma
Sarcoma - metabolism
Sarcoma - pathology
Smac
Tumors
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Summary:Second mitochondria‐derived activator of caspases (Smac/DIABLO) is released from mitochondria into the cytosol during apoptosis, promoting caspase activation by neutralizing the inhibition of inhibitor of apoptosis proteins (IAPs) on caspases. Alteration of apoptosis is essential for cancer development, and cancer cell death by radiation and chemotherapy is largely dependent upon apoptosis. In this study, archival tissues of 100 carcinomas and 50 sarcomas from various origins were analyzed by immunohistochemistry for the expression of Smac/DIABLO. Smac/DIABLO immunoreactivity was seen in 62 of 100 (62%) carcinomas, including 42 of 60 stomach carcinomas, 7 of 10 colorectal carcinomas, 4 of 10 lung carcinomas, 7 of 10 ovarian carcinomas, and 2 of 10 prostate carcinomas. Smac/DIABLO is expressed in 11 of 50 (22%) sarcomas, including 2 of 8 malignant schwannomas, 5 of 11 rhabdomyosarcomas, 2 of 7 malignant fibrous histiocytomas, 1 of 6 leiomyosarcomas, 0 of 8 angiosarcomas, 0 of 8 liposarcomas, and 1 of 2 Ewing's sarcomas. These data demonstrated that Smac/DIABLO expression levels vary depending on the individual cancer types. Furthermore, the present study showed that many human cancers do not express Smac/DIABLO, and suggest that lack of Smac/DIABLO expression in the cancer cells may inhibit apoptosis, thereby promoting their survival.
ISSN:0903-4641
1600-0463
DOI:10.1034/j.1600-0463.2003.t01-1-1110202.x