Differential gene expressions during immortalization of normal human fibroblasts and endothelial cells transfected with human telomerase reverse transcriptase gene.
It is widely accepted that telomerase, which compensates for telomere shortening, is finally activated in almost all kinds of human malignant neoplasms, and ectopic expression of telomerase may endow some kinds of human somatic cells with indefinite proliferation capacity, i.e., immortality. To clarify the intrinsic responses required in acquiring immortality, we investigated the chronological changes in the expression levels of the cell cycle and apoptosis-related genes by real-time RT-PCR in human normal fibroblasts and endothelial cells after hTERT transfection. We found that fibroblast MJ90 required intrinsic responses including reversible upregulation of cell-cycle promoting genes and down-regulation of apoptosis-inducing genes in early phase after transfection, whereas the endothelial cell HUE142-2 did not. In addition, the microarray analysis of the fibroblast strains revealed that the dysregulated genes during cellular immortalization were different from those reported in fibroblasts probably having acquired telomere maintenance mechanism concomitant with hTERT induction. These findings indicate that cell-type specific differential gene expression after telomerase activation may be important to acquire telomere-maintenance capacity and immortality in some non-cancerous human cells. Investigation of these molecules may elucidate the differences in the capacity of acquiring immortality in cancer and normal somatic cells in future.
Kumazaki
Tsutomu
T
Department of Translational Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Japan.
Hiyama
Keiko
K
Takahashi
Tomoko
T
Omatsu
Hideaki
H
Tanimoto
Keiji
K
Noguchi
Takuya
T
Hiyama
Eiso
E
Mitsui
Youji
Y
Nishiyama
Masahiko
M
D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins; D042783:Endothelial Cells / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics*; D019098:Telomerase / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection
D004268:DNA-Binding Proteins; D011506:Proteins; D019098:Telomerase