title: 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.
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.
authors.affiliation: Department of Surgery, UCLA School of Medicine 90024.
authors.forename: A S
authors.initials: AS
authors.lastname: Koo
authors.forename: R
authors.initials: R
authors.lastname: Chiu
authors.forename: J
authors.initials: J
authors.lastname: Soong
authors.forename: J B
authors.initials: JB
authors.lastname: Dekernion
authors.forename: A
authors.initials: A
authors.lastname: Belldegrun
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016758:Genes, jun / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D007680:Kidney Neoplasms / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D007375:Interleukin-1; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma