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Expression of survivin and caspase-3 in gastric cancer
J Kania1, S J Konturek, K Marlicz
1Department of Internal Medicine, University Erlangen-Nuremberg, Erlangen, Germany.
Abstract:
Gastric cancer is one of the most common malignant tumors of the gastrointestinal tract. However, the molecular pathways involved in the regulation of gastric carcinogenesis are not completely elucidated. In the last decade, basic cancer research has been focused on the deregulation of apoptosis as a central event in the process of carcinogenesis. Caspase-3 and survivin are regulators of apoptosis and have been implicated in the development of gastric cancer. The aim of the present study was to compare the expression of mRNA and protein for survivin and caspase-3 in the gastric cancer and in the cancer margin with that in normal human gastric mucosa. Fifteen patients with advanced gastric cancer (all H. pylori-positive) and 15 matched control subjects with normal gastric mucosa were included in this study. The biospy specimens for histology and for molecular analyses were taken from gastric tumor, tumor surrounding gastric mucosa and in normal patients from the mucosa of antrum and corpus. Survivin mRNA expression was very weak, but detectable, in the normal gastric mucosa. However, at the protein level, no expression for survivin was detected in the normal gastric mucosa. In the biopsy specimens from tumor and surrounding gastric mucosa, a significant increase in survivin mRNA and protein expression was observed. The expression of survivin was higher in the tumor than in the tumor margin. The mRNA and protein expression of caspase-3 was detected in the gastric mucosa of normal subjects. In gastric cancer only the expression of procaspase-3 was observed, while the expression of active caspase-3 was completely undetectable. In the gastric mucosa surrounding gastric cancer, no gene and protein expression for caspase-3 was detected. We conclude that the changes in the level of caspase-3 and survivin play an important role in the transformation from normal gastric mucosa to gastric career.
Insights
Survivin and caspase-3 levels are altered in gastric cancer. Increased survivin and decreased active caspase-3 expression in tumors suggest their role in gastric carcinogenesis, impacting apoptosis regulation.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Gastric cancer is a major gastrointestinal malignancy.
- Molecular pathways in gastric carcinogenesis are not fully understood.
- Deregulation of apoptosis is a key event in cancer development.
Purpose of the Study:
- To compare survivin and caspase-3 mRNA and protein expression.
- To analyze expression in gastric cancer, surrounding mucosa, and normal gastric mucosa.
- To investigate the role of these apoptosis regulators in gastric carcinogenesis.
Main Methods:
- Biopsy specimens from 15 advanced gastric cancer patients and 15 controls.
- Analysis of survivin and caspase-3 mRNA and protein expression.
- Comparison between tumor, tumor margin, and normal gastric mucosa.
Main Results:
- Survivin mRNA and protein expression significantly increased in tumor and surrounding mucosa compared to normal mucosa.
- Survivin expression was higher in tumor tissue than in the surrounding margin.
- Active caspase-3 was undetectable in gastric cancer and surrounding mucosa, while procaspase-3 was present. Normal mucosa showed caspase-3 expression.
Conclusions:
- Altered expression of survivin and caspase-3 is crucial in gastric carcinogenesis.
- Increased survivin and loss of active caspase-3 contribute to apoptosis evasion in gastric cancer.
- These molecular changes are vital for the progression from normal gastric mucosa to cancer.