The Study Of C/EBPβ In Tumor Suppression And Murine ES Cell Differentiation

C/EBPβ(CCAAT/enhancer-binding proteinβ), also called NF-IL6, is an important transcription factor involved in proliferation and differentiation. Firstly, our research was focused on the relationship of C/EBPβand tumor growth. Using DOTAP:Chol liposomes as a carrier, we delivered C/EBPβexpression plasmid, pCN, into nude mice bearing human colon cancer tumors via tail vein. Southern blots revealed that the pCN/liposome was capable of delivering the C/EBPβplasmid to the main organs as well as tumors. Experimental gene therapy showed that a strong suppression of tumor growth was observed in the pCN-treated mice. Such suppression was due to the overexpression of C/EBPβ, leading to the increased apoptosis in tumors of pCN-treated mice. And the apoptosis was possibly associated with the p21 (Waf1/Cip1), rather than p53, a well known upstream gene of p21.On the other hand, we investigated the role of C/EBPβin the differentiation of mouse embryonic stem cell (ES cell). By stable transfection of C/EBPβand LIP, its truncated form, into ES cells, we found that the constitutive overexpression of C/EBPβhad no effect on Oct-4 protein level under undifferentiated conditions, but could maintain the expression of Oct-4, Nanog and Sox2 for a time period significantly longer than the wild ES cells after LIF and MEF was removed from the culture. And this function of C/EBPβcould be antagonized by LIP. In addition, ES cells transfected with C/EBPβstill had the ability to form embryonic body (EB) and differentiate neuronal cells after RA induction. cDNA array on 10 d EBs revealed that fibroblast growth factors were marked by up-regulation, which suggested that C/EBPβpossibly induced ES cell differentiation by FGF pathway.Overall, C/EBPβcan suppress the growth of colon tumor in vivo; in mouse ES cells, the overexpression of exogenous C/EBPβfacilitates the maintenance of ES characters.