cDNA-library testing identifies transforming genes cooperating with c-myc in mouse pre-B cells.

摘要: While c-myc often contributes to the generation of B cell transformation, its transgenic overexpression alone does not lead full transformation B-lineage cells. Synergistically acting second genes must cooperate. Here, we constructed doxycycline-inducible cDNA-libraries from preB mRNA. These libraries were retrovirally transduced as single copies into cells and overexpressed in fetal-lived derived c-myc-overexpressing lines. We scored by survival and/or expansion differentiating vitro vivo. Only one double c-myc/cDNA-library-expressing line was found less than 5×106 library-transduced surviving expressing a cDNA-library-derived transcript vitro. This identified shortened form Exosc1 gene, encoding RNA exosome complex component CSL4. Transplantations c-myc/Exosc1 short-form- or full-length-transgenic Rag1−/− mice resulted survival, differentiation CD19+CD93−sIgM+CD5low/−CD11b+ mature B1 and, surprisingly, also vigorous Strikingly, after transplantations c-myc/cDNA-library preBI frequencies double-transgenic their differentiated progeny, expanding vivo heterogeneous phenotypes, at least 10-fold higher In first analysis Ptprcap, Cacybp, Ndufs7, Rpl18a Rpl35a identified. suggests strong influence host on transformation. This article is protected copyright. All rights reserved