Cancer Res 2001 Feb 15;61(4):1250-4
Nonet GH, Stampfer MR, Chin K, Gray JW, Collins CC, Yaswen P.
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.
This puts a pretty hard stamp of approval on human telemere length and
the limits on which cell types that express telomerase as being parts of a
genomic anti-cancer program. It also provides a possible drug target.
I expect ZNF217 is a Zinc Finger DNA binding protein that activates
telomerase meaning that one could target its degradation with ribozymes
or blocking it with antisense-RNA. Alternatively one could develop the
means to flood rapidly dividing cells with a specific decoy DNA sequence
to which it binds thereby avoiding its effects in activating the telomerase
>From an anti-aging standpoint, turning this gene on in the stem cells
remaining in an adult body could be quite useful.
Genes Dev 2001 Jan 1;15(1):50-65
Elenbaas B, et al
Human breast cancer cells generated by oncogenic transformation of primary
mammary epithelial cells.
Int J Oncol. 1998 Mar;12(3):499-507. Review.
The role of retinoblastoma and p53 tumor suppressor pathways in human
mammary epithelial cell immortalization.
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