| Full description or Abstract | Most somatic cells do not express sufficient amounts of telomerase
to maintain a constant telomere length during cycles of chromosome
replication. Consequently, there is a limit to the number of doublings
somatic cells can undergo before telomere shortening triggers
an irreversible state of cellular senescence. Ectopic expression
of telomerase overcomes this limitation, and in conjunction with
specific oncogenes can transform cells to a tumorigenic phenotype.
However, recent studies have questioned whether the stabilization
of chromosome ends entirely explains the ability of telomerase
to promote tumorigenesis and have resulted in the hypothesis that
telomerase has a second function that also supports cell division.
Here we show that ectopic expression of telomerase in human mammary
epithelial cells (HMECs) results in a diminished requirement for
exogenous mitogens and that this correlates with telomerase-dependent
induction of genes that promote cell growth. Furthermore, we show
that inhibiting expression of one of these genes, the epidermal
growth factor receptor (EGFR), reverses the enhanced proliferation
caused by telomerase. We conclude that telomerase may affect proliferation
of epithelial cells not only by stabilizing telomeres, but also
by affecting the expression of growth-promoting genes. |
| Keywords & MeSH headings | Neoplastic,Epithelial Cells,P.H.S.,Cell Transformation,enzymology,Neoplasms,Cells,Human,DNA Replication/drug effects/genetics,Growth Substances/biosynthesis/genetics,Support,Cell Aging/drug effects/genetics,genetics,Molecular Sequence Data,Cultured,metabolism,Repressor Proteins/genetics/metabolism,Mitogens/pharmacology,Receptor,RNA/analysis/genetics,Up-Regulation/drug effects/genetics,drug effects,Epidermal Growth Factor/genetics/metabolism,Gene Expression Regulation,Cell Division,Telomerase |