| Budget Amount *help |
¥47,300,000 (Direct Cost: ¥47,300,000)
Fiscal Year 2004: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 2003: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2002: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2001: ¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2000: ¥9,000,000 (Direct Cost: ¥9,000,000)
|
|---|
| Research Abstract |
Human somatic cells have a limited proliferative lifespan by telomere shortening. Telomerase is an enzyme that elongates telomere DNA at each chromosome end providing cells indefinite proliferative lifespan. However, our results suggested that telomerase participated more than that in telomerase-expressing human somatic cells. Some human somatic cells in vitro continue proliferation to the limit of telomere shortening and ceased proliferation by cellular senescence but other somatic cells cease proliferation by culture shock or premature senescence far before telomere shortening. Fibroblasts and endothelial cells were the former cases. They ceased proliferation through transduction process of signals from telomere shortening to p21 expression. Expression of p21 was p53 independent and regulated positively by p38MAPK and negatively by HDAC2. These cells were immortalized by introduction of human telomerase gene (hTERT). The latter cases were osteoblasts, astrocytes, and hepatocytes. The
… More
y proliferated to the final end of telomere erosion after the introduction of T-antigen gene whose gene product inactivates tumor suppressor gene products as p53 and RB. T-antigen introduced cells were made immortal by additional introduction of hTERT. Expectedly, osteoblasts did not extend their proliferative lifespan by introduction of hTERT alone. Immortalization of osteoblasts occurred after telomerase expression and p16 nock-down. However, unexpectedly, hTERT appeared to have such growth promoting activity as T-antigen and extended proliferative lifespan resulting immortal cells for astrocytes and hepatocytes. We searched for cellular proteins, by proteome analysis and DNA chips, that facilitated cells for continued proliferation in telomerase introduced human somatic cells. Other possible role of telomerase is on genome integrity. Telomerase-introduced human somatic cells showed resistance against chromosome aberration and integration of genetic materials. These characteristics are favor for somatic stem cells, which harbor telomerase activity, to continue proliferation during whole human lifespan and to maintain low tumorigenicity. Less
|
