The mouse tumor cell lines EL4 and RMA display mosaic expression of NK-related and certain other surface molecules and appear to have a common origin.
As a potential means for facilitating studies of NK cell-related molecules, we examined the expression of these molecules on a range of mouse tumor cell lines. Of the lines we initially examined, only EL4 and RMA expressed such molecules, both lines expressing several members of the Ly49 and NKRP1 families. Unexpectedly, several of the NK-related molecules, together with certain other molecules including CD2, CD3, CD4, CD32, and CD44, were often expressed in a mosaic manner, even on freshly derived clones, indicating frequent switching in expression. In each case examined, switching was controlled at the mRNA level, with expression of CD3zeta determining expression of the entire CD3-TCR complex. Each of the variable molecules was expressed independently, with the exception that CD3 was restricted to cells that also expressed CD2. Treatment with drugs that affect DNA methylation and histone acetylation could augment the expression of at least some of the variable molecules. The striking phenotypic similarity between EL4 and RMA led us to examine the state of their TCRbeta genes. Both lines had identical rearrangements on both chromosomes, indicating that RMA is in fact a subline of EL4. Overall, these findings suggest that EL4 is an NK-T cell tumor that may have retained a genetic mechanism that permits the variable expression of a restricted group of molecules involved in recognition and signaling.
Gays
F
F
Department of Microbiology, The Medical School, Newcastle, United Kingdom.
Unnikrishnan
M
M
Shrestha
S
S
Fraser
K P
KP
Brown
A R
AR
Tristram
C M
CM
Chrzanowska-Lightowlers
Z M
ZM
Brooks
C G
CG
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics; D001374:Azacitidine / Q000494:pharmacology; D018801:CD2 Antigens / Q000096:biosynthesis / Q000235:genetics; D017252:CD3 Complex / Q000096:biosynthesis / Q000235:genetics; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D019175:DNA Methylation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D014644:Genetic Variation / Q000276:immunology; D006657:Histones / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics; D006877:Hydroxamic Acids / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009030:Mosaicism / Q000276:immunology*; D055651:NK Cell Lectin-Like Receptor Subfamily B; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D055630:Receptors, NK Cell Lectin-Like; D014407:Tumor Cells, Cultured
D000950:Antigens, Ly; D000954:Antigens, Surface; D018801:CD2 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D006657:Histones; D018960:Hyaluronan Receptors; D006877:Hydroxamic Acids; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; C012589:trichostatin A; D001374:Azacitidine