Silva S, Wang Y, Babonits M, Axelson H, Wiener F, Klein G
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Curr Top Microbiol Immunol. 1992;182:251-9. doi: 10.1007/978-3-642-77633-5_31.
Mouse plasmacytomas (MPC) carry one of three reciprocal translocations that juxtapose c-myc to one of the three immunoglobulin (Ig) loci. Here we describe an exceptional MPC, induced by pristane oil and Abelson (A-MuLV) virus. It does not carry any of the three c-myc/Ig translocations, but contains a previously unknown reciprocal T(6;12) translocation affecting the bands known to carry the IgK (6C/1) and N-myc (12B) loci, respectively. Northern blot analysis showed high N-myc but no c-myc expression. This is consistent with the constitutive activation of N-myc by a juxtaposition of the IgK and N-myc loci. Reciprocal translocation in B-cell derived tumors are believed to involve the Ig loci by the action of some enzyme that participates in the physiological rearrangement of the Ig loci. Only transcriptionally active chromatin regions are accessible to such recombinases (Alt et al. 1987). N-myc is not expressed in B-cells, but it is transcriptionally active during the early pro- and pre-B cell stage, whereafter it and the surrounding chromatin region becomes inactive (Smith et al. 1992). It is therefore most likely that the N-myc/Kappa translocation has arisen at an early stage of B-cell differentiation. This would imply that the myc/Ig translocations do not block B-cell differentiation. They also reaffirm the functional equivalence of N- and c-myc in relation to B-cell carcinogenesis, as shown by our previous work on tumor induction in N-myc transgenic mice (Wang et al. 1992).
小鼠浆细胞瘤(MPC)携带三种相互易位中的一种,该易位使c-myc与三个免疫球蛋白(Ig)基因座之一并列。在此,我们描述一种由 pristane 油和 Abelson(A-MuLV)病毒诱导产生的特殊MPC。它不携带三种c-myc/Ig易位中的任何一种,而是包含一种先前未知的相互T(6;12)易位,该易位分别影响已知携带IgK(6C/1)和N-myc(12B)基因座的条带。Northern印迹分析显示N-myc高表达但无c-myc表达。这与IgK和N-myc基因座并列导致N-myc的组成型激活一致。B细胞来源肿瘤中的相互易位被认为是通过某种参与Ig基因座生理重排的酶的作用而涉及Ig基因座。只有转录活性染色质区域才能被这种重组酶作用(Alt等人,1987年)。N-myc在B细胞中不表达,但在早期前B细胞和前B细胞阶段具有转录活性,此后它和周围的染色质区域变得无活性(Smith等人,1992年)。因此,N-myc/Kappa易位很可能发生在B细胞分化的早期阶段。这意味着myc/Ig易位不会阻断B细胞分化。它们还再次证实了N-myc和c-myc在B细胞致癌作用方面的功能等效性,正如我们之前在N-myc转基因小鼠肿瘤诱导研究中所表明的那样(Wang等人,1992年)。