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.
Douvdevani
A
A
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Huleihel
M
M
Segal
S
S
Apte
R N
RN
D016475:3T3 Cells; D000199:Actins / Q000235:genetics; D000818:Animals; D000906:Antibodies; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000502:physiology; D016258:Genes, mos; D016259:Genes, myc; D011905:Genes, ras; D007375:Interleukin-1 / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
D000199:Actins; D000906:Antibodies; D007375:Interleukin-1; D012333:RNA, Messenger