| First Author | Sharpless NE | Year | 2003 |
| Journal | Oncogene | Volume | 22 |
| Issue | 32 | Pages | 5055-9 |
| PubMed ID | 12902988 | Mgi Jnum | J:85075 |
| Mgi Id | MGI:2671661 | Doi | 10.1038/sj.onc.1206809 |
| Citation | Sharpless NE, et al. (2003) Both products of the mouse Ink4a/Arf locus suppress melanoma formation in vivo. Oncogene 22(32):5055-9 |
| abstractText | Deletion of the INK4a/ARF locus at 9p21 is detected with high frequency in human melanoma. Within a short genomic distance, this locus encodes several proteins with established tumor-suppressor roles in a broad spectrum of cancer types. Several lines of evidence support the view that p16INK4a and p19ARF exert the tumor-suppressor activities of this locus, although their relative importance in specific cancer types such as melanoma has been less rigorously documented on the genetic level. Here, we exploit a well-defined mouse model of RAS-induced melanomas to examine the impact of germline p16INK4a or p19ARF nullizygosity on melanoma formation. We demonstrate that loss of either Ink4a/Arf product can cooperate with RAS activation to produce clinically indistinguishable melanomas. In line with the common phenotypic end point, we further show that RAS+ p16INK4a-/- melanomas sustain somatic inactivation of p19ARF-p53 and, correspondingly, that RAS+ p19ARF-/- melanomas experience high-frequency loss of p16INK4a. These genetic studies provide definitive proof that p16INK4a and p19ARF cooperate to suppress the development of melanoma in vivo. |
