The ZNF217 gene amplified in breast cancers promotes immortalization of human mammary epithelial cells

The functional consequences of overexpression of a candidate oncogene on ch romosome 20q13.2, ZNF217, were examined by transducing the gene into finite life span human mammary epithelial cells (HMECs). In four independent expe riments, ZNF217-transduced cultures gave rise to immortalized cells. HMECs that overcame senescence initially exhibited heterogeneous growth and conti nued telomere erosion, followed by increasing telomerase activity, stabiliz ation of telomere length, and resistance to transforming growth factor beta growth inhibition. The incremental changes in telomerase activity and grow th that occurred in ZNF217-transduced cultures after they overcame senescen ce were similar to the conversion pattern we have described previously in r are HMEC lines immortalized after exposure to a chemical carcinogen. Aberra nt expression of ZNF217 may be selected for during breast cancer progressio n because it allows breast cells to overcome senescence and attain immortal ity.