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Role of tumor metastasis suppressor gene KAI1 in digestive tract carcinomas and cancer cells

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Abstract

The KAI1 gene is identified as a tumor metastasis suppressor gene in many types of cancer. We examined KAI1 gene and its protein KAI1/CD82 expression by in situ hybridization and immunohistochemical analysis, and found that KAI1 mRNA and protein expression were inversely correlated with lymph node and distant metastasis in digestive tract carcinomas, but not with age and gender of the patient, or with tumor differentiation. Moreover, KAI1/CD82 protein expression positively reflected the survival outcome of patients. Western blot analysis showed that VP-16 increased KAI1/CD82 protein expression obviously in various cancer cell lines, especially in those that were highly metastatic. This increased KAI1/CD82 expression was associated with its translocation from the cytomembrane to the nucleus, in which it interacted with nuclear p53 protein, forming a strong complex, observed by confocal microscopy and co-immunoprecipitation, respectively. In nude mice, after feeding with VP-16, the number of tumors metastasized from spleen to liver was obviously reduced, and KAI1/CD82 protein expression became stronger in those metastatic tumors. Accordingly, this demonstrated that KAI1 might be used as an indicator for predicting the clinical outcome, and VP-16 may be clinically considered as a promising candidate for anti-metastasis with regard to its potential to upregulate KAI1 expression.

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Author notes

  1. Ming-qing Zhang

    Present address: Dong Nan Hospital, Fujian Province, China

  2. Yu-qiang Chen

    Present address: 174 Hospital, Fujian Province, China

Authors and Affiliations

  1. Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, 361005, Xiamen, Fujian Province, China

    Qiao Wu, Yuan Ji, Ming-qing Zhang, Yu-qiang Chen, Yu-qiang Chen, Fu Chen, Da-lin Shi, Zong-hui Zheng, Yao-jian Huang & Wen-jin Su

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  1. Qiao Wu
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  2. Yuan Ji
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Correspondence to Qiao Wu.

Additional information

The study was supported by the Key Project of Science & Technology of the Ministry of Education (00073), the National High Technology Research and Development Program of China (Program 863, grant 2001AA620401), the National Natural Science Foundation of China (grants 39880015, 30170477), and the National Outstanding Youth Science Foundation of China (grant 39825502).

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Wu, Q., Ji, Y., Zhang, Mq. et al. Role of tumor metastasis suppressor gene KAI1 in digestive tract carcinomas and cancer cells. Cell Tissue Res 314, 237–249 (2003). https://doi.org/10.1007/s00441-003-0781-6

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  • DOI: https://doi.org/10.1007/s00441-003-0781-6

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