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Oncogene. 2000 May 25;19(23):2780-5.

Angiogenesis is an early event in the generation of myc-induced lymphomas.

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Fred Hutchinson Cancer Research Center, Seattle, Washington, WA 98109-1024, USA.


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).

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