C/EBPα基因与肿瘤

C/EBPα基因是抑癌基因,有抑制增殖、促进分化和调节DNA损伤反应等作用。各种机制如对抗性的蛋白质-蛋白质相互作用、基因突变和翻译后修饰等导致C/EBPα转录抑制或活性丧失,可能诱发肿瘤。本文结合国内外研究现状,介绍C/EBPα基因的结构、功能及与肿瘤的诊断、治疗和预后的关系。     

Increase in CD30 ligand/CD153 and TNF-α expressing mast cells in basal cell carcinoma

Mast cells are a significant source of tumor necrosis factor (TNF) superfamily members, such as TNF-α, CD30 ligand/CD153 (CD30L) and CD40L/CD154. Furthermore, the expression of some of these proteins in mast cells has been associated with tumorigenesis, and mast cells have been found to be increased in number in the basal cell carcinoma (BCC) lesion. In this study, we have examined the expression of TNF-α, CD30L and CD40L immunoreactivity in mast cells in the healthy-looking skin and lesional skin of ten patients with superficial spreading BCC. Also, the counterparts of these molecules, TNF receptor (TNFR) I and II as well as CD30 and CD40, were analysed immunohistochemically. We found that numbers of mast cells and Kit-positive cells were significantly increased in the dermal BCC lesion. The percentage of CD30L-positive mast cells and the number of CD30-positive cells were significantly increased in the upper dermis of the BCC lesion as well. In addition, the numbers of TNF-α-positive mast cells and cells with TNFRI and TNFRII were markedly increased in the upper lesional dermis. In contrast, no mast cells positive for CD40L could be detected, even though the lesional dermis contained increased numbers of CD40 positive cells. The BCC epithelium was positive for TNFRI, TNFRII and CD40, but not for CD30, though the larger basal buds appeared to be less intensely stained for TNFRI and CD40. In conclusion, mast cells positive for CD30L and TNF-α, but not CD40L, are increased in number in the lesional dermis in BCC. These data suggest plausible pathways whereby mast cells can be activated and to interact with other cells and thereby contribute to the tumorigenesis in BCC.     

Fine particulate matter (PM2.5) enhances FcεRI-mediated signaling and mast cell function

Persistent exposure to ambient fine particulate matter (PM_2.5) can exacerbate allergic diseases in humans. Mast cells play an important role in allergic inflammation in peripheral tissues, such as skin, mucosa, and lung. Engagement of the high-affinity Fc receptor leads to mast cell degranulation, releasing a variety of highly active mediators including histamine, leukotrienes, and inflammatory cytokines. How PM_2.5 exposure affects mast cell activation and function remains largely unknown. To characterize the effect of PM_2.5 on mast cells, we used bone marrow-derived mast cells (BMMCs) to examine whether PM_2.5 affected FcεRI-mediated signaling, cytokine production, and degranulation. Exposure to high doses of PM_2.5 caused pronounced apoptosis and death of BMMCs. In contrast, exposure to low doses of PM_2.5 enhanced mast cell degranulation and FcεRI-mediated cytokine production. Further analysis showed that PM_2.5 treatment increased Syk activation and subsequently phosphorylation of its substrates including LAT, PLC-γ1, and SLP-76. Moreover, PM_2.5 treatment led to activation of the PI3K and MAPK pathways. Intriguingly, water-soluble fraction of PM_2.5 were found responsible for the enhancement of FcεRI-mediated signaling, mast cell degranulation, and cytokine production. Our data suggest that PM_2.5, mainly water-soluble fraction of PM_2.5, could affect mast cell activation through enhancing FcεRI-mediated signaling.