ARF mutation accelerates pituitary tumor development in Rb+/− mice
AUTOR(ES)
Tsai, Kenneth Y.
FONTE
National Academy of Sciences
RESUMO
Mice heterozygous for the retinoblastoma (Rb) tumor suppressor gene develop pituitary and thyroid tumors with high penetrance. We demonstrate here that loss of the ARF tumor suppressor strongly accelerates intermediate lobe pituitary tumorigenesis in Rb heterozygous mice. These effects in the pituitary are greater than those conferred by p53 loss in that Rb+/−;ARF−/− mice display significantly more early atypical lesions than Rb+/−; p53−/− mice. Also, Rb+/−;ARF−/− compound mutants do not develop many of the novel tumors or precancerous lesions seen in Rb+/−;p53−/− compound mutants. Although complete loss of ARF expression is not obligatory for pituitary tumorigenesis in Rb+/− mice, alterations of the ARF locus are observed in tumors from Rb+/−;ARF+/− mice, consistent with a selective advantage of ARF inactivation in this context. We conclude that inactivation of ARF acts more broadly than that of p53 in connecting abrogation of the Rb pathway to tumorigenesis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=139235Documentos Relacionados
- RB-mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung metastases in Rb+/− mice
- Loss of Caveolin-1 Gene Expression Accelerates the Development of Dysplastic Mammary Lesions in Tumor-Prone Transgenic Mice
- The Arf tumor suppressor gene promotes hyaloid vascular regression during mouse eye development
- p107 is a suppressor of retinoblastoma development in pRb-deficient mice
- Expression of the Arf tumor suppressor gene is controlled by Tgfβ2 during development