Down-regulation of LFA-1 adhesion receptors by C-myc oncogene in human B lymphoblastoid cells.
The function of the c-myc gene and its role in tumorigenesis are poorly understood. In order to elucidate the role of c-myc oncogene activation in B cell malignancy, the phenotypic changes caused by the expression of c-myc oncogenes in human B lymphoblastoid cells immortalized by Epstein-Barr virus were analyzed. C-myc oncogenes caused the down-regulation of lymphocyte function-associated antigen-1 (LFA-1) adhesion molecules (alpha L/beta 2 integrin) and loss of homotypic B cell adhesion in vitro. Down-regulation of LFA-1 occurred by (i) posttranscriptional modulation of LFA-1 alpha L-chain RNA soon after acute c-myc induction, and (ii) transcriptional modulation in cells that chronically express c-myc oncogenes. Analogous reductions in LFA-1 expression were detectable in Burkitt lymphoma cells carrying activated c-myc oncogenes. Since LFA-1 is involved in B cell adhesion to cytotoxic T cells, natural killer cells, and vascular endothelium, these results imply functions for c-myc in normal B cell development and lymphomagenesis.
Inghirami
G
G
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Grignani
F
F
Sternas
L
L
Lombardi
L
L
Knowles
D M
DM
Dalla-Favera
R
R
D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D015849:Plasminogen Inactivators; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D011519:Proto-Oncogenes
D016169:Lymphocyte Function-Associated Antigen-1; D015849:Plasminogen Inactivators; D016271:Proto-Oncogene Proteins c-myc