期刊
EUROPEAN JOURNAL OF CANCER
卷 45, 期 3, 页码 321-327出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2008.11.020
关键词
Proto-oncogene Hck; Src family kinase; Podosome; Phagocytes; Chronic myeloid leukaemia
类别
资金
- la Ligue Nationale contre le Cancer
- Association pour la Recherche contre le Cancer (ARC) [3988]
- ARC-Institut National du Cancer (INCA)
Hck is a phagocyte specific proto-oncogene of the Src family expressed as two isoforms, p59Hck and p61Hck. It plays a critical role in Bcr/Abl-chronic myeloid leukaemia and is able to transform fibroblasts in vitro. However, the tumourigenic activity of Hck and the respective oncogenic functions of Hck isoforms have not been examined. Tet-Off fibroblasts expressing constitutively active mutants of p59Hck and p61Hck together or individually were used. In contrast to cells expressing p59Hck(ca) or p61Hck(ca) alone, cells expressing both isoforms were transformed in vitro and induced tumour formation in 90% of nude mice within 2 weeks. This is the first demonstration of (i) the tumourigenic activity of Hck in mice, (ii) the cooperative action of the two Hck isoforms in vitro and in vivo. To our knowledge, this is the first example of a transforming activity 'split' in two requisite isoforms. (C) 2008 Elsevier Ltd. All rights reserved.
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