Ras oncogene transformation of human B lymphoblasts is associated with lymphocyte activation and with a block of differentiation.
The p21ras small GTP binding proteins participate in signal transduction from cell surface receptors and affect neoplastic transformation and development in many different cell types. In the present study, we examined the relationship between ras transformation and differentiation of human B lymphocytes. We show that the constitutive expression of the T24 Ha-ras oncogene in EBV-immortalized B lymphoblasts was associated with the induction of the interleukin 2 receptor alpha subunit, with an impaired immunoglobulin gene expression, altered adhesion properties and increased survival in serum-free medium. Since induction of the IL-2 receptor alpha subunit is a hallmark of lymphocyte activation, we suggest that p21ras naturally triggers B cell activation. The ras-transformed lymphocytes displayed a fully functional IL-2r, as assessed by c-fos induction following treatment with IL-2; nevertheless, they were not growth stimulated by this lymphokine. The decreased expression of immunoglobulin genes indicates that the ras oncogene blocks terminal differentiation to plasma cells, possibly by inhibiting the activity of lymphocyte-specific transcription factors. Somewhat unexpectedly, the constitutive p21ras activity did not cause an increased DNA binding of transcription factors PEA1 (AP1), PEA3, Oct-2 or NF-kB.
Sirinian
M I
MI
Centro Acidi Nucleici C.N.R., Università La Sapienza, Rome, Italy.
Marchetti
A
A
Di Rocco
G
G
Starace
G
G
Jucker
R
R
Nasi
S
S
D001402:B-Lymphocytes / Q000473:pathology*; D001483:Base Sequence; D002454:Cell Differentiation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000378:metabolism; D016762:Genes, fos; D011905:Genes, ras; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis
D007376:Interleukin-2; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D015375:Receptors, Interleukin-2; D004247:DNA