Interferon-α activates multiple STAT signals and down-regulates c-Met in primary human hepatocytes

A proteomic analysis reveals the loss of expression of the cell death regulatory gene GRIM-19 in human renal cell carcinomas

“…Indeed, the expression of c-met a factor that promotes RCC growth is directly induced by STAT3 (Klosek et al, 2004;Trovato et al, 2004;Yang et al, 2005). IFN-a, a recommended therapeutic for RCC (Cohen and McGovern, 2005), inhibits the expression of met (Radaeva et al, 2002). In this study, we have clearly shown that the expression of GRIM-19, the other known inhibitor of STAT3, is inhibited in primary RCCs.…”

Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation

“…Cell extract preparation and Western blot analysis were performed as described previously. 23 Cell Culture and Proliferation. Primary mouse hepatocyte culture and [ 3 H]thymidine (1 Ci per well) uptake were performed as described previously.…”

“…Primary mouse hepatocyte culture and [ 3 H]thymidine (1 Ci per well) uptake were performed as described previously. 23 Cell proliferation was also determined by BrdU labeling, measured by a cell proliferation enzyme-linked immunosorbent assay kit (Roche, Penzberg, Germany). The relative BrdU incorporation was expressed as absorbance (A370 nm -A492 nm ).…”

Regulation of c-met expression by transcription repressor Daxx

“…First, Pax3 and Ets1 activate c-met transcription (Epstein et al, 1996;Gambarotta et al, 1996), while Daxx represses Pax3 and Ets1 transactivation (Hollenbach et al, 1999;Li et al, 2000b). Second, IFNa upregulates Daxx (Shimoda et al, 2002) that may lead to the observed downregulation of c-met expression upon IFNa treatment (Radaeva et al, 2002). Third, p53 activation of the c-met promoter correlates with demonstrated interaction of p53 with Daxx (Kim et al, 2003;Ohiro et al, 2003;Zhao et al, 2003), and potential sequestration of Daxx repression activity through this interaction.…”

“…The cmet gene is regulated by a high GC-content TATA-less promoter (Seol and Zarnegar, 1998); several transcription factors including Sp1, Smad, p53, Ets1, Pax3, AP1 were shown as positive regulators of this promoter (Epstein et al, 1996;Gambarotta et al, 1996;Seol et al, 1999;Zhang et al, 2005); HIF-1 activates c-met upon hypoxia (Pennacchietti et al, 2003), while oxidative stress and IFNa are negative regulators presumably via inhibition of Sp1 binding (Radaeva et al, 2002;Zhang and Liu, 2003). The complexity of c-met regulation, together with apparent correlation between c-Met protein level and carcinogenesis, points to the necessity of an additional study of c-met expression control.…”