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 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.
Yoo
Nam Jin
NJ
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Kim
Hong Sug
HS
Kim
Su Young
SY
Park
Won Sang
WS
Park
Cho Hyun
CH
Jeon
Hae  Myung
H
Jung
Eun Sun
ES
Lee
Jung Young
JY
Lee
Sug Hyung
SH
D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D012509:Sarcoma / Q000378:metabolism* / Q000473:pathology
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins