THE ACTIVATED ANAPLASTIC LYMPHOMA KINASE INCREASES CELLULAR PROLIFERATION AND ONCOGENE UP-REGULATION IN RAT 1A FIBROBLASTS

作者: Axel Wellmann , Victoria Doseeva , Wayne Butscher , Mark Raffeld , Paula Fukushima

DOI: 10.1096/FASEBJ.11.12.9337149

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摘要: More than 60% of anaplastic large-cell lymphomas (Ki-1 lymphoma) are associated with a t(2;5)(p23;q35) translocation that produces an 80 kDa hyperphosphorylated chimeric protein (p80) derived from the fusion lymphoma kinase (ALK) nucleophosmin (NPM). The NPM-ALK gene is activated tyrosine has been shown to be potent oncogene. We have developed cellular model for study p80 action in rat 1a fibroblasts. Expression cDNA's encoding fibroblasts induces anchorage-independent growth soft agar and promotes foci formation culture. Cells expressing exogenous showed significantly increased proliferation characterized by accelerated cell cycle entry into S-phase. Consistent G0/G1 S-phase transition, there also marked up-regulation cyclin A D1 expression. In addition, transformed cells elevated expression several immediate early genes involved proliferation, includ...

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