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

• Main Authors: Papadopoulos Nikoletta, Sonnenschein Carlos, Soto Ana M, Maffini Maricel V, Theoharides Theoharis C
• Format: Article
• Language: English
• Published: BMC 2008-04-01
• Series: Cancer Cell International
• Online Access: http://www.cancerci.com/content/8/1/5

<p>Abstract</p> <p>Background</p> <p>c-<it>kit </it>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-<it>kit </it>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 <it>c-kit </it>in mammary carcinogenesis in the Ws/Ws rats carrying spontaneous lack-of-function mutation in the c-<it>kit </it>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p>