Primary research

Lack of c-kit receptor promotes mammary tumors in N-nitrosomethylurea-treated Ws/Ws rats

Maricel V. Maffini , Ana M. Soto , Carlos Sonnenschein , Nikoletta Papadopoulos and Theoharis C. Theoharides

Cancer Cell International 2008, 8:5doi:10.1186/1475-2867-8-5

Published:	29 April 2008

Abstract (provisional)

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 50mg/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.