Aberrations in interleukin-1 expression in oncogene-transformed fibrosarcoma lines: constitutive interleukin-1 alpha transcription and manifestation of biological activity

We have examined interleukin-1 (IL-1) expression in a series of oncogene-transformed NIH-3T3 fibroblastoid cell lines. In contrast to primary fibroblasts where IL-1 is inducible, NIH-3T3 cells (clone 490N3T) transcribe the IL-1 alpha gene constitutively. Transformation of 490N3T cells by the v-mos or v-H-ras oncogenes appears to either enhance or suppress IL-1 alpha transcription, respectively. In v-myc transfected cells, constitutive IL-1 activity could be detected intracellularly. An additional membrane-associated form of IL-1 was observed in lines transformed by protein-kinase (PK) encoding oncogenes, such as TPR-met, c-met, v-src, v-abl, v-mos and v-raf. In none of the lines tested the secreted form of IL-1 activity could be detected, and no constitutive expression of IL-1 beta was observed. Our studies manifest aberrations in IL-1 expression in oncogene-transformed fibroblastoid cell lines, detected at different regulatory levels, such as transcription, translation and compartmentalization. IL-1 is a potent pleiotropic cytokine, with regard to its target cell specificity and spectrum of activities; growth promoting effects of IL-1 on fibroblasts were reported and on the other hand this cytokine activates various anti-tumor mechanisms. Thus, endogenous IL-1 expression by tumor cells may affect the neoplastic phenotype, either by influencing the growth of the malignant cells or by modifying tumor-host interactions.