CD24, a signal-transducing molecule expressed on human B cells, is a major surface antigen on small cell lung carcinomas.
Cell lines derived from human small cell carcinoma of the lung express high levels of a surface polypeptide termed the cluster-w4 antigen, which was previously identified as a potential target for toxin-based immunotherapy of lung cancer. We have cloned a complementary DNA encoding the cluster-w4 antigen from COS-1 fibroblasts transfected with a SW2 small cell carcinoma library, by panning with a mixture of the cluster-w4-specific monoclonal antibodies SWA11, SWA21, and SWA22. The sequence of the cluster-w4 complementary DNA encodes an unusually short (80-amino acid) protein identical to that recently reported for the leukocyte activation molecule CD24 except for a single valine-alanine substitution due to a single-base polymorphism within the region of the gene coding for the extracellular domain. Biochemical analyses of the cloned cluster-w4 antigen confirmed both the presence of the phosphatidylinositol tail and the extensive glycosylation reported for the CD24 molecule. Furthermore, the cloned cluster-w4 antigen expressed on COS cells was shown to react with a comprehensive panel of CD24-specific monoclonal antibodies, as assessed by indirect immunofluorescence staining. Northern blot hybridization indicated the presence of several transcript sizes for the cluster-w4 antigen that were greatly overexpressed in small cell carcinoma cell lines, compared with normal hemopoietic cells and CD24-positive cell lines. Southern blot hybridization of restriction digests of genomic DNA identified a complex pattern of bands consistent with either a complex gene structure containing many exons or the presence of a family of closely related genes.
Jackson
D
D
Molecular Immunology Group, John Radcliffe Hospital, Oxford, UK.
Waibel
R
R
Weber
E
E
Bell
J
J
Stahel
R A
RA
D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000502:physiology; D000954:Antigens, Surface / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D001483:Base Sequence; D051927:CD24 Antigen; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000276:immunology*; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D008970:Molecular Weight; D017385:Sequence Homology; D015398:Signal Transduction / Q000502:physiology*; D014633:Valine / Q000235:genetics
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D051927:CD24 Antigen; C497889:CD24 protein, human; C497890:Cd24a protein, mouse; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D014633:Valine; D000409:Alanine