The Expression of C-Jun and Junb mRNA in Renal Cell Cancer and in Vitro Regulation by Transforming Growth Factor Beta 1 and Tumor Necrosis Factor Alpha 1

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Abstract
The proto-oncogene C-jun acts as a transcriptional activator or repressor for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. JunB inhibits c-jun's transforming activities. We investigated the expression of jun genes in renal cell cancer (RCC) and their regulation by cytokines and transforming growth factor beta 1 (TGF-b1). The constitutive expression of c-jun was detected in 39 of 43 fresh frozen RCC, 5 of 10 normal kidneys, and the expression of junB detected in 28 of 34 RCC, 5 of 6 normal kidneys. C-jun was also found expressed in all 10 RCC tumor lines examined and junB was expressed at low levels in 6 of 10 renal tumor lines. TGF-b1 and tumor necrosis factor alpha (TNF-a) have been shown to alter the expression of jun genes in other tissue types. Additionally, TGF-b1, TNF-a, and gamma interferon (g-IFN) were shown to inhibit the growth of RCC. We found that TGF-b1 highly augmented the expression of junB (mean of 34 folds, p less than .05), but did not significantly alter the expression of c-jun, the transforming gene. In contrast, TNF-a significantly enhanced the expression of both c-jun (mean fold enhancement of 2.1, p less than .05) and junB (2.2 folds, p less than .05). Interleukin-2 (IL-2), interleukin-4 (IL-4) and g-IFN did not significantly alter jun expression. The findings presented suggest that c-jun may have a role in inducing malignant transformation in RCC and a novel mechanism by which TGF-b1 may exert its anti-tumor effects, via the activation of junB. Additionally, although TGF-b1, TNF-a, and g-IFN all have anti-proliferative actions on RCC in vitro, they were found to have different effects in altering jun expressions.