Brandvold K A, Neiman P, Ruddell A
Fred Hutchinson Cancer Research Center, Seattle, Washington, WA 98109-1024, USA.
Oncogene. 2000 May 25;19(23):2780-5. doi: 10.1038/sj.onc.1203589.
Angiogenesis was identified as an early consequence of myc gene overexpression in two models of retroviral lymphomagenesis. Avian leukosis virus (ALV) induces bursal lymphoma in chickens after proviral c-myc gene integration, while the HB-1 retrovirus carries a v-myc oncogene and also induces metastatic lymphoma. Immunohistochemical studies of the effects of increased c-myc or v-myc overexpression revealed early angiogenesis within myc-transformed bursal follicles, which persisted in lymphomas and metastases. Abnormal vessel growth was consistently detected within 13 days after transplantation of a few myc-overexpressing progenitors into ablated bursal follicles, suggesting that these angiogenic changes may support the initial expansion of tumor precursors, as well as later stage lymphomagenesis. Conditioned media from myc-overexpressing B cell lines promoted proliferation of vascular endothelium in vitro, while media from B cells expressing low myc levels showed little effect. Moreover, ectopic myc overexpression in the low myc B cell lines increased production of the endothelial growth activity, indicating that myc induces secretion of angiogenic factors from B cells. These findings demonstrate that myc overexpression in lymphocytes generates an angiogenic phenotype in vitro as well as in vivo. Oncogene (2000).
在两种逆转录病毒淋巴瘤发生模型中，血管生成被确定为myc基因过表达的早期结果。禽白血病病毒（ALV）在原病毒c-myc基因整合后可诱导鸡的法氏囊淋巴瘤，而HB-1逆转录病毒携带v-myc癌基因，也可诱导转移性淋巴瘤。对c-myc或v-myc过表达增加的影响进行的免疫组织化学研究显示，在myc转化的法氏囊滤泡内有早期血管生成，这种血管生成在淋巴瘤和转移灶中持续存在。将少数过表达myc的祖细胞移植到消融的法氏囊滤泡后13天内，始终检测到异常的血管生长，这表明这些血管生成变化可能支持肿瘤前体细胞的初始扩增以及后期淋巴瘤的发生。来自过表达myc的B细胞系的条件培养基在体外促进血管内皮细胞增殖，而来自低水平表达myc的B细胞的培养基则几乎没有作用。此外，在低表达myc的B细胞系中异位过表达myc可增加内皮生长活性的产生，表明myc可诱导B细胞分泌血管生成因子。这些发现表明，淋巴细胞中myc的过表达在体外和体内均产生血管生成表型。《癌基因》（2000年）
