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Expression of a splice variant of KAI1, a tumor metastasis suppressor gene, influences tumor invasion and progression.
- Source :
-
Cancer research [Cancer Res] 2003 Nov 01; Vol. 63 (21), pp. 7247-55. - Publication Year :
- 2003
-
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.
- Subjects :
- Adenocarcinoma metabolism
Adenocarcinoma pathology
Alternative Splicing
Animals
Biomarkers, Tumor biosynthesis
Biomarkers, Tumor genetics
Cadherins metabolism
Cell Division physiology
Cell Line, Tumor
Colonic Neoplasms metabolism
Colonic Neoplasms pathology
Disease Progression
Extracellular Matrix metabolism
Extracellular Matrix pathology
Genes, Tumor Suppressor
Humans
Integrin alpha3beta1 metabolism
Kangai-1 Protein
Membrane Glycoproteins genetics
Membrane Glycoproteins metabolism
Mice
Prognosis
RNA, Messenger biosynthesis
RNA, Messenger genetics
Stomach Neoplasms genetics
Antigens, CD
Membrane Glycoproteins biosynthesis
Proto-Oncogene Proteins
Stomach Neoplasms metabolism
Stomach Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 63
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 14612520