Chk2*1100delC 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*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.
Meyer
Sara E
SE
Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, OH 45267, USA.
Peace
Belinda E
BE
Bahassi
El Mustapha
el M
Kavanaugh
Gina M
GM
Wagh
Purnima K
PK
Robbins
Susan B
SB
Yin
Moying
M
Wells
Susanne I
SI
Zinser
Glendon M
GM
Stambrook
Peter J
PJ
Waltz
Susan E
SE
D000818:Animals; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D064447:Checkpoint Kinase 2; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology; D051379:Mice; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion
D064447:Checkpoint Kinase 2; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases; C578634:CHEK2 protein, human; C578633:Chek2 protein, mouse; D017346:Protein Serine-Threonine Kinases