title: Lack of c-kit receptor promotes mammary tumors in N-nitrosomethylurea-treated Ws/Ws rats.
abstract: BACKGROUND
  c-kit is expressed in various cell types during development and it has been linked to the promotion of cellular migration, proliferation and/or survival of melanoblasts, hematopoietic progenitors and primordial germ cells. Several reports have proposed a role for the c-kit gene on carcinogenesis. Gain-of-function mutations are associated with diseases such as mastocytosis and gastrointestinal stromal tumors among others. However, very little is known about pathologies associated with loss-of-function mutations. Regarding breast cancer, c-kit protein and mRNA are highly expressed in normal breast but their expression decreases or is absent in the presence of breast cancer. We studied the role of c-kit in mammary carcinogenesis in the Ws/Ws rats carrying spontaneous lack-of-function mutation in the c-kit gene. Fifty day-old virgin female Ws/Ws rats and their wild type counterparts were injected with either 50 mg/kg body weight of the chemical carcinogen N-nitrosomethylurea or with vehicle. The animals were followed-up for 6 months. Fisher 344 rats were used as positive controls for tumor development.
  
  
  RESULTS
  Eleven weeks after treatment, palpable tumors were detected in the Ws/Ws rats. The tumor incidence was 80% in Ws/Ws rats, while no tumors were observed in the wild type rats (p = 0.006). Our data show that the lack of c-kit is permissive for the development of mammary tumor in Ws/Ws rats treated with carcinogen.
  
  
  CONCLUSIONS
  We conclude that the lack of c-kit may contribute to an imbalanced homeostatic state in the mammary gland either by affecting signaling between stroma and epithelium, or through the lack of mast cells.
authors.affiliation: Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, USA. maricel.maffini@tufts.edu
authors.forename: Maricel V
authors.initials: MV
authors.lastname: Maffini
authors.forename: Ana M
authors.initials: AM
authors.lastname: Soto
authors.forename: Carlos
authors.initials: C
authors.lastname: Sonnenschein
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides