Frequent downregulation of the KAI1(CD82) metastasis suppressor protein in human cancer cell lines.
KAI1 is a metastasis suppressor gene on human chromosome 11p11.2 that encodes a glycoprotein of the transmembrane four superfamily. Reduced KAI1 expression associates with malignant progression of human prostatic, lung and pancreatic cancers, but the role of KAI1 protein in the malignant progression of other human cancers remains to be elucidated. We analysed KAI1 protein in normal and cancer cells of the prostate, ovary, bladder, endometrium, lung and melanocytes by Western blot to determine if KAI1 may be involved in multiple cancers. We also investigated the relationship of KAI1 expression and two other transmembrane four superfamily proteins, CD81 and CD9, in the cells. We found that KAI1 protein was downregulated in 31/42 of the cancer cell lines analysed. Alternatively, some ovarian, bladder and endometrial cells had distinct, heterogeneous KAI1 protein band patterns in Western blots that were due primarily to N-linked glycosylation. Most of the cancer cells expressed two other transmembrane four superfamily proteins, CD81 and CD9. Downregulation of KAI1 protein may be an indicator of metastatic potential in cancers of urogenital, gynecological, and pulmonary origin and in melanomas. KAI1 may also have post-translational modifications specific to tissue type or malignant progression.
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
A
A
White
P W
PW
Lamb
J C
JC
Barrett
D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D051861:Kangai-1 Protein; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins; D009362:Neoplasm Metastasis / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C554798:CD81 protein, human; C497688:CD82 protein, human; C554869:CD9 protein, human; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D060225:Tetraspanin 28; D060245:Tetraspanin 29