Genetic interaction between Rb and N-ras: differentiation control and metastasis.

The retinoblastoma tumor suppressor gene, Rb, and the ras proto-oncogenes regulate various cellular processes, including differentiation and proliferation. Rb and ras genetically interact to positively influence differentiation in the mouse. This genetic interaction between Rb and ras also affects tumor development, either positively or negatively depending on cell type. Loss of one or two N-ras alleles allows medullary thyroid (C cell) adenomas occurring in Rb heterozygous mice to progress to metastatic carcinomas, an event associated with C cells displaying a less-differentiated phenotype. Here, we discuss the genetic interaction between Rb and ras and the development of a mouse model of medullary thyroid carcinoma.