Chk21100delC Acts in synergy with the Ron receptor tyrosine kinase to accelerate mammary tumorigenesis in mice

The CHEK2 (Chk2 in mice) polymorphic variant, CHEK2*1100delC, leads to genomic instability and is associated with an increased risk for breast cancer. The Ron receptor tyrosine kinase is overexpressed in a large fraction of human breast cancers. Here, we asked whether the low penetrance Chk2*1100del...

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Bibliographic Details
Published in:Cancer letters 2010-10, Vol.296 (2), p.186-193
Main Authors: Meyer, Sara E., Peace, Belinda E., Bahassi, El Mustapha, Kavanaugh, Gina M., Wagh, Purnima K., Robbins, Susan B., Yin, Moying, Wells, Susanne I., Zinser, Glendon M., Stambrook, Peter J., Waltz, Susan E.
Format: Article
Language:English
Subjects:
Animals
Breast cancer
Breast Neoplasms - epidemiology
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell Cycle
Cell Division
Cell Line, Tumor
Checkpoint Kinase 2
CHEK2
DNA damage
Family medical history
Female
Genetic Variation
Hepatocyte growth factor-like protein (HGFL)
Humans
Immunohistochemistry
Kinases
Mammary Neoplasms, Animal - genetics
Mammary Neoplasms, Animal - pathology
Met receptor
Mice
MST1R
Polymorphism, Genetic
Protein-Serine-Threonine Kinases - genetics
Receptor Protein-Tyrosine Kinases - genetics
Receptor tyrosine kinase
Risk Factors
Rodents
Sequence Deletion
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Summary:The CHEK2 (Chk2 in mice) polymorphic variant, CHEK2*1100delC, leads to genomic instability and is associated with an increased risk for breast cancer. The Ron receptor tyrosine kinase is overexpressed in a large fraction of human breast cancers. Here, we asked whether the low penetrance Chk2*1100delC allele alters the tumorigenic efficacy of Ron in the development of mammary tumors in a mouse model. Our data demonstrate that Ron overexpression on a Chk2*1100delC background accelerates the development of mammary tumors, and shows that pathways mediated by a tyrosine kinase receptor and a regulator of the cell cycle can act to hasten tumorigenesis in vivo.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2010.04.011