Abstract：
:KAI1 (CD82) belongs to the transmembrane 4 superfamily in which members have inhibitory effects on tumor cell motility and metastasis. During reverse transcription-PCR analysis, we found a splice variant of KAI1 (spliced-KAI1) in which exon 7 was deleted. This exon encodes the 28 amino acids that span from the distal part of the second extracellular loop to the proximal part of the fourth transmembrane region. Expression of spliced-KAI1 was observed in metastatic tissues of gastric cancer patients with poor prognosis after operation. Genomic DNA analysis revealed that this variant was derived from the alternative splicing of exon 7. Immunoprecipitation showed that the interaction of spliced-KAI1 with integrin alpha(3)beta(1) was weaker than that of wild-type KAI1. Wild-type KAI1, but not spliced-KAI1, colocalized with E-cadherin, an adherens junction protein. Also, mouse colon adenocarcinoma cells stably expressing spliced-KAI1 (CT-26/spliced-KAI1) showed increased in vivo tumorigenicity, as well as increased in vitro invasive potential and cell-extracellular matrix adhesion compared with wild-type KAI1-expressing cells. In metastatic lung and liver tissues from mice inoculated with CT-26/spliced-KAI1 cells, the expression of wild-type KAI1 was nearly absent and spliced-KAI1 was dominant, and weak interaction of KAI1 with integrin alpha(3)beta(1) was observed. These results indicate that there is a functional difference between wild-type KAI1 and spliced-KAI1 in respect to cell motility, adhesion, tumor growth and metastasis, and expression of spliced-KAI1 may be a marker for poor prognostic factors in gastric and other cancers.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Lee JH,Seo YW,Park SR,Kim YJ,Kim KKsubject
Has Abstractpub_date
2003-11-01 00:00:00pages
7247-55issue
21eissn
0008-5472issn
1538-7445journal_volume
63pub_type
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