Understanding the exact combinations of genetic mutations that produce human cancers is important to developing selective and specific treatments that target the cancerous cells and spare the normal cells. Yu et al. created mice in which the cyclin D1 gene was disrupted along with oncogenic version of either c-myc, v-H-ras, c-neu, or Wnt-1. Mice carrying these oncogenes in a wild-type cyclin D1 background develop spontaneous breast cancers. However, cyclin D1 was essential specifically for tumors arising from oncogenic Neu or Ras, but not Myc or Wnt-1. The underlying mechanism was that Neu and Ras appear to regulate progression through the cell cycle selectively in mammary tissue, but not other tissues, by inducing the expression of only cyclin D1. In tumors from other tissues with oncogenic Neu or Ras, or in tumors with oncogenic Myc or Wnt-1, cyclin D1 and D2 are both activated. As discussed by Bartek and Lukas, these results provide direct evidence that cancers in different tissues do arise from specific and unique combinations of genetic mutations, and at least in principle, treatments could be developed to target specific cancers.
Q. Yu, Y. Geng, P. Sicinski, Specific protection against breast cancers by cyclin D1 ablation. Nature 411, 1017-1021 (2001). [Online Journal]
J. Bartek, J. Lukas, Are all cancer genes equal? Nature 411, 1001-1002 (2001). [Online Journal]