Role of p21WAF1/CIP1 as an attenuator of both proliferative and drug-induced apoptotic signals in BCR-ABL-transformed hematopoietic cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-03

AUTHORS

Karin Forster, Axel Obermeier, Olga Mitina, Nicola Simon, Markus Warmuth, Günter Krause, Michael Hallek

ABSTRACT

The constitutive tyrosine kinase activity of the BCR-ABL fusion protein plays a crucial role in the pathogenesis of chronic myeloid leukemia and promotes growth factor-independent survival of hematopoietic cells. In 32D cells, expression levels of retrovirally transduced BCR-ABL were positively correlated with the levels of the cell cycle regulator protein p21, and this upregulation of p21 expression depended on the kinase activity of BCR-ABL. To assess the role of p21 on BCR-ABL-positive hematopoietic cells, we compared proliferation and drug-induced apoptosis in bone marrow (BM) cells from wild-type and p21 knockout mice after retroviral transfer of the BCR-ABL fusion gene. As compared with wild-type cells, p21 knockout cells showed increased proliferation, suggesting that p21 acted as an attenuator of BCR-ABL-mediated cell proliferation. In marked contrast, deletion of p21 promoted apoptosis induction by imatinib and taxol in BCR-ABL-transformed BM cells. These findings demonstrate that p21 has a dual function in BCR-ABL-transformed murine BM cells: It attenuates the effects of two apparently opposed phenomena such as BCR-ABL-mediated cell proliferation and drug-induced apoptosis. This dual function of p21 calls for a cautious evaluation of the suitability of p21 as a secondary target in anticancer therapy. More... »

PAGES

183-193

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00277-007-0400-9

    DOI

    http://dx.doi.org/10.1007/s00277-007-0400-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1012340813

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17960378


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