Abstract
Bcr-Abl is a constitutively active tyrosine kinase that is expressed in Philadelphia chromosome (Ph1)-positive human leukemias. Bcr-Abl has been shown to inhibit apoptosis and cause anchorage independent growth. However, its ability to activate mitogenic signaling pathways is controversial. Here we show that Bcr-Abl signaling prevents down-regulation of cyclin-dependent kinase activity and cell cycle arrest after growth factor deprivation of hematopoietic progenitor cells. Using an inducible system to regulate Bcr-Abl expression, we also demonstrate that Bcr-Abl expression is sufficient to induce G1-to-S phase transition, DNA synthesis, and activation of cyclin-dependent kinases in cells that were arrested in G0 by growth factor deprivation. Furthermore, Bcr-Abl activates Ras, Erk, and Jnk pathways as a primary consequence of expression. These data show that Bcr-Abl is one of a select group of oncogenes that is capable of both inhibiting apoptosis and deregulating cell proliferation. The combination of these activities is likely to be important for the progression of CML.
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Cortez, D., Reuther, G. & Pendergast, A. The Bcr-Abl tyrosine kinase activates mitogenic signaling pathways and stimulates G1-to-S phase transition in hematopoietic cells. Oncogene 15, 2333–2342 (1997). https://doi.org/10.1038/sj.onc.1201400
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DOI: https://doi.org/10.1038/sj.onc.1201400
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