Id2 deficiency promotes metastasis in a mouse model of ocular cancer

The inhibitor of DNA binding 2 (Id2) basic helix-loop-helix protein interacts genetically and physically with the pocket proteins (Rb, p107 and p130) and has been implicated as an oncogene. In other studies, however, Id2 has been shown to function as a tumor suppressor. Here, we studied the role of Id2 in a well characterized model of ocular cancer in which the three pocket proteins are inactivated by generating mice lacking one or both Id2 alleles. Id2 deficiency had no impact on tumorigenesis in the eye. Unexpectedly, however, Id2 loss significantly increased the rate of metastasis. Liver metastases in Id2 heterozygotes demonstrated significant decrease of Id2 expression and loss of the remaining Id2 allele, strongly suggesting that Id2 inactivation specifically was required for metastasis in this model. These findings provide new insights into the role of Id2 in metastasis.