Differentially expressed genes throughout the cellular immortalization processes are quite different between normal human fibroblasts and endothelial cells.
It is widely accepted that activation of telomerase and maintenance of telomeres play central roles in cellular immortalization for most cancer cells. However, they seem to be insufficient for normal human cells. To elucidate critically responsible genes for telomerase mediated cellular immortalization in non-cancerous cells, we explored the genes that are differentially expressed throughout the immortalization process of normal human cells using cDNA microarrays with novel normalization procedures. We found that the number of genes, differentially expressed during cellular immortalization after ectopic expression of telomerase, dramatically increased in a later phase, especially in fibroblasts. We identified 18 and 20 genes/ESTs dysregulated throughout the cellular immortalization processes in fibroblasts and endothelial cells, respectively, but none of them overlapped. Only BGN and COL5A2 were commonly downregulated, except for at early phase in fibroblasts, and a few genes showed controversial expression changes, with regard to previous reports in cancer cells. These findings indicate that normal somatic cells would require cell-type specific events in addition to telomerase activation, and a rare population that eventually experience such events would acquire immortality. The key molecules that distinguish the immortalization mechanisms in cancerous and non-cancerous cells may become crucial targets for anticancer therapy and regenerative therapy.
Hiyama
Keiko
K
Department of Translational Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-ku, Japan. khiyama@hiroshima-u.ac.jp
Otani
Keiko
K
Ohtaki
Megu
M
Satoh
Kenichi
K
Kumazaki
Tsutomu
T
Takahashi
Tomoko
T
Mitsui
Youji
Y
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
Omatsu
Hideaki
H
Noguchi
Takuya
T
Tanimoto
Keiji
K
Nishiyama
Masahiko
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004789:Enzyme Activation; D020224:Expressed Sequence Tags; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism; D014162:Transfection
D000970:Antineoplastic Agents; D018076:DNA, Complementary; D012333:RNA, Messenger; D012313:RNA; D019098:Telomerase