Role of tumor metastasis suppressor gene KAI1 in digestive tract carcinomas and cancer cells.
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.
Wu
Qiao
Q
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. xgwu@xmu.edu.cn
Ji
Yuan
Y
Zhang
Ming-qing
MQ
Chen
Yu-qiang
YQ
Chen
Fu
F
Shi
Da-lin
DL
Zheng
Zong-hui
ZH
Huang
Yao-jian
YJ
Su
Wen-jin
WJ
D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D051861:Kangai-1 Protein; D008099:Liver / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; C497688:CD82 protein, human; C497689:Cd82 antigen, mouse; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D019384:Nucleic Acid Synthesis Inhibitors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D005047:Etoposide