Hilbert D M, Theisen P W, Rudikoff E K, Bauer S R
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Oncogene. 1998 Oct 22;17(16):2125-35. doi: 10.1038/sj.onc.1202134.
After in vivo inoculation with abl/myc- and raf/myc-containing retroviruses, BALB/c mice predominantly develop late stage B cell tumors (plasmacytomas) and less frequently develop earlier B-lineage tumors while DBA/2 mice do not develop B-lineage tumors. We have investigated the in vitro tumorigenic potential of these viruses using cultured normal pre-B cell lymphocytes from both BALB/c and DBA/2 mice. Interestingly, both viruses infect cultured pre-B lymphocytes from both mouse strains. Following infection, IL-7 dependent pre-B cells become independent of normal in vitro growth requirements within 24 h and can rapidly form in vivo pre-B lymphomas in both mouse strains. Mechanisms mediating loss of IL-7 dependence are different depending on whether the raf or abl gene is present in myc-containing viruses. IL-7 JAK-STAT signaling is constitutively active in abl/myc induced pre-B cell tumors. In contrast, IL-7 JAK-STAT signaling is not constitutive in raf/myc induced pre-B cell tumors, demonstrating that subversion of this component of IL-7 signal transduction is not obligatory for pre-B cell transformation or loss of IL-7 dependence.
用含abl/myc和raf/myc的逆转录病毒进行体内接种后，BALB/c小鼠主要发生晚期B细胞肿瘤（浆细胞瘤），较少发生早期B谱系肿瘤，而DBA/2小鼠不发生B谱系肿瘤。我们使用来自BALB/c和DBA/2小鼠的培养正常前B细胞淋巴细胞，研究了这些病毒的体外致瘤潜力。有趣的是，两种病毒都能感染来自这两种小鼠品系的培养前B淋巴细胞。感染后，依赖IL-7的前B细胞在24小时内变得不依赖正常的体外生长需求，并能在两种小鼠品系中迅速形成体内前B淋巴瘤。介导IL-7依赖性丧失的机制因含myc的病毒中是否存在raf或abl基因而有所不同。IL-7 JAK-STAT信号在abl/myc诱导的前B细胞肿瘤中持续激活。相比之下，IL-7 JAK-STAT信号在raf/myc诱导的前B细胞肿瘤中不是组成性的，这表明IL-7信号转导的这一成分的颠覆对于前B细胞转化或IL-7依赖性丧失不是必需的。
