The ZNF217 gene amplified in breast cancers promotes immortalization of human mammary epithelial cells.
The functional consequences of overexpression of a candidate oncogene on chromosome 20q13.2, ZNF217, were examined by transducing the gene into finite life span human mammary epithelial cells (HMECs). In four independent experiments, ZNF217-transduced cultures gave rise to immortalized cells. HMECs that overcame senescence initially exhibited heterogeneous growth and continued telomere erosion, followed by increasing telomerase activity, stabilization of telomere length, and resistance to transforming growth factor beta growth inhibition. The incremental changes in telomerase activity and growth that occurred in ZNF217-transduced cultures after they overcame senescence were similar to the conversion pattern we have described previously in rare HMEC lines immortalized after exposure to a chemical carcinogen. Aberrant expression of ZNF217 may be selected for during breast cancer progression because it allows breast cells to overcome senescence and attain immortality.
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
G H
GH
Nonet
M R
MR
Stampfer
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K
Chin
J W
JW
Gray
C C
CC
Collins
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P
Yaswen
D001940:Breast / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D006801:Humans; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D014161:Transduction, Genetic
D015534:Trans-Activators; C113698:ZNF217 protein, human; D019098:Telomerase