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Brief inactivation of c-Myc is not sufficient for sustained regression of c-Myc-induced tumours of pancreatic islets and skin epidermis

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Pelengaris, Stella, Abouna, Sylvie, Cheung, Linda, Ifandi, Vasiliki, Zervou, Sevasti I. and Khan, Michael (2004) Brief inactivation of c-Myc is not sufficient for sustained regression of c-Myc-induced tumours of pancreatic islets and skin epidermis. BMC Biology, Vol.2 (No.26). doi:10.1186/1741-7007-2-26

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Official URL: http://dx.doi.org/10.1186/1741-7007-2-26

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Abstract

Background
Tumour regression observed in many conditional mouse models following oncogene inactivation provides the impetus to develop, and a platform to preclinically evaluate, novel therapeutics to inactivate specific oncogenes. Inactivating single oncogenes, such as c-Myc, can reverse even advanced tumours. Intriguingly, transient c-Myc inactivation proved sufficient for sustained osteosarcoma regression; the resulting osteocyte differentiation potentially explaining loss of c-Myc's oncogenic properties. But would this apply to other tumours?

Results
We show that brief inactivation of c-Myc does not sustain tumour regression in two distinct tissue types; tumour cells in pancreatic islets and skin epidermis continue to avoid apoptosis after c-Myc reactivation, by virtue of Bcl-xL over-expression or a favourable microenvironment, respectively. Moreover, tumours progress despite reacquiring a differentiated phenotype and partial loss of vasculature during c-Myc inactivation. Interestingly, reactivating c-Myc in β-cell tumours appears to result not only in further growth of the tumour, but also re-expansion of the accompanying angiogenesis and more pronounced β-cell invasion (adenocarcinoma).

Conclusions
Given that transient c-Myc inactivation could under some circumstances produce sustained tumour regression, the possible application of this potentially less toxic strategy in treating other tumours has been suggested. We show that brief inactivation of c-Myc fails to sustain tumour regression in two distinct models of tumourigenesis: pancreatic islets and skin epidermis. These findings challenge the potential for cancer therapies aimed at transient oncogene inactivation, at least under those circumstances where tumour cell differentiation and alteration of epigenetic context fail to reinstate apoptosis. Together, these results suggest that treatment schedules will need to be informed by knowledge of the molecular basis and environmental context of any given cancer.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH): Tumour regression, Tumors -- Growth, Oncogenes
Journal or Publication Title: BMC Biology
Publisher: BioMed Central Ltd.
ISSN: 1741-7007
Official Date: 21 December 2004
Dates:
DateEvent
21 December 2004Published
Volume: Vol.2
Number: No.26
DOI: 10.1186/1741-7007-2-26
Status: Peer Reviewed
Access rights to Published version: Open Access
Funder: Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Association for International Cancer Research (AICR)

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