Abstract
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 p59Hckca or p61Hckca 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.
Keywords
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Article info
Publication history
Published online: December 29, 2008
Accepted:
November 6,
2008
Received in revised form:
October 27,
2008
Received:
June 2,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.