title: Chk2*1100delC Acts in synergy with the Ron receptor tyrosine kinase to accelerate mammary tumorigenesis in mice.
abstract: 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.
authors.affiliation: Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, OH 45267, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Meyer
authors.forename: Belinda E
authors.initials: BE
authors.lastname: Peace
authors.forename: El Mustapha
authors.initials: el M
authors.lastname: Bahassi
authors.forename: Gina M
authors.initials: GM
authors.lastname: Kavanaugh
authors.forename: Purnima K
authors.initials: PK
authors.lastname: Wagh
authors.forename: Susan B
authors.initials: SB
authors.lastname: Robbins
authors.forename: Moying
authors.initials: M
authors.lastname: Yin
authors.forename: Susanne I
authors.initials: SI
authors.lastname: Wells
authors.forename: Glendon M
authors.initials: GM
authors.lastname: Zinser
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Stambrook
authors.forename: Susan E
authors.initials: SE
authors.lastname: Waltz
mesh_terms: 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
chemical_list: 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