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Human stomach-specific gene, CA11, is down-regulated in gastric cancer
K Shiozaki1, S Nakamori, M Tsujie
1Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Abstract:
To reveal the implication in gastric cancer pathogenesis of the novel human gene referred to as CA11, which was recently isolated by a differential display technique using normal gastric mucosa and gastric cancer tissue, we examined CA11 expression in 50 primary gastric cancers and also introduced the CA11 gene into gastric cancer cells. RNA dot blot analysis against various human organs and developmental stages demonstrated that CA11 was intensively expressed especially in normal stomach tissue. Northern blot analysis showed that expression of the CA11 gene in cancer tissue was down-regulated compared with normal tissue. Semi-quantitative RT-PCR also demonstrated that CA11 gene expression was decreased in 41 out of 50 (82%) of the gastric cancer tissues, when compared with normal stomach tissues, while no relationship was found between CA11 expression and various clinicopathological characteristics including histological type, depth of invasion, lymph node metastasis, and clinical stage. Immunohistochemical analysis with anti CA11 antibody showed that CA11-positive staining was observed in the surface regions of normal gastric epithelium, but was found faintly or not at all in cancer tissues. CA11 transfected MKN28 cells also displayed a marked decrease in the number of colony formations when compared to double normal controls. These findings suggest that the loss of CA11 expression in gastric tissues may play an important role in gastric carcinogenesis.
Insights
The novel CA11 gene is highly expressed in normal stomach tissue but significantly down-regulated in most gastric cancers. Loss of CA11 expression may contribute to gastric cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- A novel human gene, CA11, was recently identified using differential display.
- CA11's role in gastric cancer pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the expression patterns of CA11 in gastric cancer.
- To determine the functional implications of CA11 in gastric cancer cells.
Main Methods:
- RNA dot blot and Northern blot analyses were used to assess CA11 expression in various human tissues and developmental stages.
- Semi-quantitative RT-PCR and immunohistochemistry were employed to evaluate CA11 expression in 50 primary gastric cancers and normal stomach tissues.
- CA11 gene was introduced into gastric cancer cells (MKN28) to assess its functional role.
Main Results:
- CA11 exhibited intensive expression in normal stomach tissue.
- CA11 gene expression was significantly down-regulated in 82% of gastric cancer tissues compared to normal tissues.
- Immunohistochemistry revealed CA11-positive staining in normal gastric epithelium but faint or absent staining in cancer tissues.
- CA11 transfection into gastric cancer cells led to a marked decrease in colony formation.
Conclusions:
- Down-regulation of CA11 expression is a frequent event in gastric cancer.
- Loss of CA11 expression may play a crucial role in gastric carcinogenesis.
- CA11 might function as a tumor suppressor in the stomach.
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