Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor.
Document Type
Article
Publication Date
2006
Keywords
Adenoma, Amides, Animals, Carcinoma-Medullary, Corticotropin, Enzyme-Inhibitors, Genes-ras, Heterozygote, Mice-Mutant-Strains, Mice-Nude, Neoplasm-Metastasis, Neuroendocrine-Tumors, Pyridines, Research-Support-N, I, H, -Extramural, Research-Support-Non-U, S, -Gov't, Retinoblastoma-Protein, Signal-Transduction, Thyroid-Neoplasms
First Page
118
Last Page
123
JAX Source
Nat Genet 2006 Jan; 38(1):118-23.
Abstract
Mutations in the gene encoding the retinoblastoma tumor suppressor predispose humans and mice to tumor development. Here we have assessed the effect of Nras loss on tumor development in Rb1 heterozygous mice. Loss of one or two Nras alleles is shown to significantly reduce the severity of pituitary tumors arising in Rb1(+/-) animals by enhancing their differentiation. By contrast, C-cell thyroid adenomas occurring in Rb1(+/-) mice progress to metastatic medullary carcinomas after loss of Nras. In Rb1(+/-)Nras(+/-) animals, distant medullary thyroid carcinoma metastases are associated with loss of the remaining wild-type Nras allele. Loss of Nras in Rb1-deficient C cells results in elevated Ras homolog family A (RhoA) activity, and this is causally linked to the invasiveness and metastatic behavior of these cells. These findings suggest that the loss of the proto-oncogene Nras in certain cellular contexts can promote malignant tumor progression.
Recommended Citation
Takahashi C,
Contreras B,
Iwanaga T,
Takegami Y,
Bakker A,
Bronson RT,
Noda M,
Loda M,
Hunt JL,
Ewen ME.
Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor. Nat Genet 2006 Jan; 38(1):118-23.