Levy L S, Lobelle-Rich P A, Overbaugh J, Abkowitz J L, Fulton R, Roy-Burman P
Department of Microbiology and Immunology SL-38, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Virology. 1993 Oct;196(2):892-5. doi: 10.1006/viro.1993.1553.
The flvi-2 locus is a target of insertional mutagenesis in thymic lymphosarcomas induced by feline leukemia virus (FeLV). flvi-2 encodes the gene bmi-1, whose product is implicated as a myc-collaborator in the induction of B- and T-cell lymphoma. We have examined the involvement of flvi-2 and myc in natural and experimentally induced FeLV-positive feline lymphosarcomas which are heterogeneous in anatomical origin, geographic origin, and strain of FeLV involved. We further compared these findings with previous reports of novel FeLV env genes in the same tumors. The results show that proviral insertion at flvi-2 occurs commonly in natural and experimental feline thymic lymphosarcomas of diverse origins [52% overall], and that alterations in c-myc commonly accompany insertional mutagenesis of flvi-2 [54% overall]. However, 46% of tumors with flvi-2 insertions apparently lack involvement of c-myc. These observations support the hypothesis that interruption of flvi-2 may be an early event in a multistep cascade, one possibility for completion of which is activation of c-myc. Interruption of flvi-2 was not observed in nonthymic lymphosarcomas of alimentary or multicentric origin, although c-myc may be involved. A proportion of both thymic and nonthymic tumors have been shown previously to contain FeLV proviruses with recombinant or mutant env genes. Our findings strongly implicate the insertional mutagenesis of flvi-2, the activation of c-myc, and the emergence of novel env genes in FeLV-mediated lymphomagenesis, particularly in the induction of thymic lymphosarcoma. The data show that these events may overlap, but do not necessarily occur concurrently.
flvi - 2基因座是猫白血病病毒（FeLV）诱导的胸腺淋巴肉瘤中插入诱变的靶点。flvi - 2编码bmi - 1基因，其产物被认为是B细胞和T细胞淋巴瘤诱导过程中的一种与myc协同作用的因子。我们研究了flvi - 2和myc在自然发生的以及实验诱导的FeLV阳性猫淋巴肉瘤中的作用，这些淋巴肉瘤在解剖学起源、地理起源以及所涉及的FeLV毒株方面具有异质性。我们进一步将这些发现与之前关于同一肿瘤中新型FeLV env基因的报道进行了比较。结果表明，flvi - 2处的前病毒插入在多种来源的自然和实验性猫胸腺淋巴肉瘤中普遍存在[总体为52%]，并且c - myc的改变通常伴随flvi - 2的插入诱变[总体为54%]。然而，46%的flvi - 2插入肿瘤显然没有c - myc的参与。这些观察结果支持了这样一种假说，即flvi - 2的中断可能是多步骤级联反应中的早期事件，完成该级联反应的一种可能性是c - myc的激活。在消化道或多中心起源的非胸腺淋巴肉瘤中未观察到flvi - 2的中断，尽管c - myc可能参与其中。先前已表明，一定比例的胸腺和非胸腺肿瘤含有具有重组或突变env基因的FeLV前病毒。我们的研究结果强烈表明，flvi - 2的插入诱变、c - myc的激活以及新型env基因的出现与FeLV介导的淋巴瘤发生有关，特别是在胸腺淋巴肉瘤的诱导过程中。数据表明，这些事件可能重叠，但不一定同时发生。
