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Immunohistochemical analysis of Smac/DIABLO expression in human carcinomas and sarcomas
Nam Jin Yoo1, Hong Sug Kim, Su Young Kim
1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Abstract:
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.
Insights
Second mitochondria-derived activator of caspases (Smac/DIABLO) expression varies in human cancers. Many cancers lack Smac/DIABLO, potentially inhibiting apoptosis and promoting tumor survival.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Death Pathways
Background:
- Second mitochondria-derived activator of caspases (Smac/DIABLO) is crucial for apoptosis by counteracting inhibitor of apoptosis proteins (IAPs).
- Apoptosis regulation is vital in cancer development and is a key mechanism for chemotherapy and radiation efficacy.
Purpose of the Study:
- To investigate the expression patterns of Smac/DIABLO in a diverse range of human carcinomas and sarcomas.
- To explore the potential correlation between Smac/DIABLO expression and cancer cell survival.
Main Methods:
- Immunohistochemistry was utilized to analyze Smac/DIABLO expression in archival tissue samples.
- The study included 100 carcinomas and 50 sarcomas from various anatomical origins.
Main Results:
- Smac/DIABLO immunoreactivity was detected in 62% of carcinomas and 22% of sarcomas analyzed.
- Expression levels of Smac/DIABLO varied significantly across different cancer types.
- A notable proportion of human cancers exhibited no Smac/DIABLO expression.
Conclusions:
- Smac/DIABLO expression is heterogeneous across various human malignancies.
- The absence of Smac/DIABLO in cancer cells may contribute to impaired apoptosis and enhanced tumor cell survival.
- These findings suggest Smac/DIABLO as a potential biomarker or therapeutic target in oncology.