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Smac/DIABLO expression in human gastrointestinal carcinoma: Association with clinicopathological parameters and survivin expression.

Shintani M, Sangawa A, Yamao N, Kamoshida S - Oncol Lett (2014)

Bottom Line: Additionally, a correlation was found between the expression of Smac/DIABLO and nuclear survivin in well- to moderately-differentiated colorectal adenocarcinomas (r=0.245; P<0.01).Conversely, the expression levels of microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker, and survivin were significantly higher in colon cancer than in gastric cancer (P<0.0001 and P<0.01, respectively).Taken together, these results indicate that not only LC3 and survivin expression, but also Smac/DIABLO expression, are significantly higher in colorectal carcinoma than in gastric carcinoma.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142, Japan.

ABSTRACT
Lack of apoptosis is a key factor in carcinogenesis and tumor progression. Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) is an antagonist of IAPs. Recently, Smac/DIABLO was identified as a potent therapeutic target. However, the clinical significance of Smac/DIABLO in gastrointestinal carcinomas remains unclear. In the present study, Smac/DIABLO expression was analyzed by immunohistochemistry in 72 gastric adenocarcinomas and 78 colorectal adenocarcinomas. The expression of Smac/DIABLO was significantly higher in colorectal carcinoma than in gastric carcinoma. Additionally, a correlation was found between the expression of Smac/DIABLO and nuclear survivin in well- to moderately-differentiated colorectal adenocarcinomas (r=0.245; P<0.01). Based on these results, it was hypothesized that gastric and colorectal carcinomas differ in the level of Smac/DIABLO expression. Our previous studies revealed that the expression of cleaved caspase-9 was significantly lower in colorectal carcinoma than in gastric carcinoma (P<0.0001). Conversely, the expression levels of microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker, and survivin were significantly higher in colon cancer than in gastric cancer (P<0.0001 and P<0.01, respectively). Taken together, these results indicate that not only LC3 and survivin expression, but also Smac/DIABLO expression, are significantly higher in colorectal carcinoma than in gastric carcinoma. We hypothesize that the analysis of Smac/DIABLO, survivin and LC3 expression in colorectal carcinoma is likely to aid cancer therapy due to the involvement of these markers in apoptosis and/or autophagy.

No MeSH data available.


Related in: MedlinePlus

Immunhistochemical staining of Smac/DIABLO in gastrointestinal carcinomas. Smac/DIABLO immunoreactivity was predominantly observed in the cytoplasm. (A) High expression of Smac/DIABLO in gastric carcinoma. (B) Low expression of Smac/DIABLO in gastric carcinoma. (C) High expression of Smac/DIABLO in rectal carcinoma. (D) Low expression of Smac/DIABLO in rectal carcinoma. Smac/DIABLO, second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI. (A–D, magnification, ×200).
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f1-ol-08-06-2581: Immunhistochemical staining of Smac/DIABLO in gastrointestinal carcinomas. Smac/DIABLO immunoreactivity was predominantly observed in the cytoplasm. (A) High expression of Smac/DIABLO in gastric carcinoma. (B) Low expression of Smac/DIABLO in gastric carcinoma. (C) High expression of Smac/DIABLO in rectal carcinoma. (D) Low expression of Smac/DIABLO in rectal carcinoma. Smac/DIABLO, second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI. (A–D, magnification, ×200).

Mentions: Smac/DIABLO expression was predominantly observed in the cytoplasm (Fig. 1). Smac/DIABLO-positive staining was observed in 46% (33/72) of gastric carcinomas. Smac/DIABLO expression was higher in well- to moderately-differentiated specimens (50%) compared with poorly-differentiated specimens (42%), however, no significant differences were identified (Table I).


Smac/DIABLO expression in human gastrointestinal carcinoma: Association with clinicopathological parameters and survivin expression.

Shintani M, Sangawa A, Yamao N, Kamoshida S - Oncol Lett (2014)

Immunhistochemical staining of Smac/DIABLO in gastrointestinal carcinomas. Smac/DIABLO immunoreactivity was predominantly observed in the cytoplasm. (A) High expression of Smac/DIABLO in gastric carcinoma. (B) Low expression of Smac/DIABLO in gastric carcinoma. (C) High expression of Smac/DIABLO in rectal carcinoma. (D) Low expression of Smac/DIABLO in rectal carcinoma. Smac/DIABLO, second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI. (A–D, magnification, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214500&req=5

f1-ol-08-06-2581: Immunhistochemical staining of Smac/DIABLO in gastrointestinal carcinomas. Smac/DIABLO immunoreactivity was predominantly observed in the cytoplasm. (A) High expression of Smac/DIABLO in gastric carcinoma. (B) Low expression of Smac/DIABLO in gastric carcinoma. (C) High expression of Smac/DIABLO in rectal carcinoma. (D) Low expression of Smac/DIABLO in rectal carcinoma. Smac/DIABLO, second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI. (A–D, magnification, ×200).
Mentions: Smac/DIABLO expression was predominantly observed in the cytoplasm (Fig. 1). Smac/DIABLO-positive staining was observed in 46% (33/72) of gastric carcinomas. Smac/DIABLO expression was higher in well- to moderately-differentiated specimens (50%) compared with poorly-differentiated specimens (42%), however, no significant differences were identified (Table I).

Bottom Line: Additionally, a correlation was found between the expression of Smac/DIABLO and nuclear survivin in well- to moderately-differentiated colorectal adenocarcinomas (r=0.245; P<0.01).Conversely, the expression levels of microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker, and survivin were significantly higher in colon cancer than in gastric cancer (P<0.0001 and P<0.01, respectively).Taken together, these results indicate that not only LC3 and survivin expression, but also Smac/DIABLO expression, are significantly higher in colorectal carcinoma than in gastric carcinoma.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142, Japan.

ABSTRACT
Lack of apoptosis is a key factor in carcinogenesis and tumor progression. Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) is an antagonist of IAPs. Recently, Smac/DIABLO was identified as a potent therapeutic target. However, the clinical significance of Smac/DIABLO in gastrointestinal carcinomas remains unclear. In the present study, Smac/DIABLO expression was analyzed by immunohistochemistry in 72 gastric adenocarcinomas and 78 colorectal adenocarcinomas. The expression of Smac/DIABLO was significantly higher in colorectal carcinoma than in gastric carcinoma. Additionally, a correlation was found between the expression of Smac/DIABLO and nuclear survivin in well- to moderately-differentiated colorectal adenocarcinomas (r=0.245; P<0.01). Based on these results, it was hypothesized that gastric and colorectal carcinomas differ in the level of Smac/DIABLO expression. Our previous studies revealed that the expression of cleaved caspase-9 was significantly lower in colorectal carcinoma than in gastric carcinoma (P<0.0001). Conversely, the expression levels of microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker, and survivin were significantly higher in colon cancer than in gastric cancer (P<0.0001 and P<0.01, respectively). Taken together, these results indicate that not only LC3 and survivin expression, but also Smac/DIABLO expression, are significantly higher in colorectal carcinoma than in gastric carcinoma. We hypothesize that the analysis of Smac/DIABLO, survivin and LC3 expression in colorectal carcinoma is likely to aid cancer therapy due to the involvement of these markers in apoptosis and/or autophagy.

No MeSH data available.


Related in: MedlinePlus