Expression of Protooncogenes during Lymphocyte Activation by Growth Factors

E. G. Bulanova,^1,2 V. M. Budagyan,¹ A. A. Yarilin,¹ and N. N. Mazurenko³

¹Institute of Immunology, Russian Ministry of Health Care, Kashirskoe Shosse 24/2, Moscow, 115478 Russia; fax: (7-095) 117-1027.

²To whom correspondence should be addressed.

³Institute of Carcinogenesis, Blokhin Oncology Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, Moscow, 115478 Russia.

Submitted March 31, 1997; revision submitted June 16, 1997.

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Effects of growth factors of non-immune origin including somatotropin (ST) and platelet-derived growth factor (PDGF) on the expression of the proteins encoded by c-fos, c-myc, c-fun, and c-ets family protooncogenes were studied for the first time. The dynamics of the oncoprotein expression in activated CD3+-lymphocytes was investigated by immunoblotting. The accumulation of the Fos and Myc proteins was enhanced in T-lymphocytes treated with ST, PDGF, or phytohemagglutinin; the accumulation was maximum at 30-60 min and decreased in 2 h; the data indicate that the oncoproteins participate in the early lymphocyte activation by various growth factors. The Jun protein appears only in 3 h after the onset of lymphocyte activation; this suggests independent participation of Fos in the early stages of lymphocyte activation prior to the appearance of Jun, preceding the joint action of Fos and Jun within the AP-1 transcription complex. The products of the c-ets family are differentially activated by the studied growth factors. Resting lymphocytes actively accumulate the Ets-1 protein; ST and PDGF activation decreases Ets-1 expression in 2 h. The Ets-2 protein is not detected in resting cells and PDGF-activated lymphocytes, whereas lymphocyte activation by ST is associated with accumulation of Ets-2. The data suggest that the product of the c-ets-1 gene is more important in the regulation of resting cells and the product of the c-ets-2 gene is important during activation of lymphocytes by ST. The results indicate that activation of lymphocytes with growth factors of non-immune origin is mediated by several signal transduction pathways.

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KEY WORDS: lymphocyte activation, protooncogene, Myc, AP-1, Ets-1, Ets-2.

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