| Project/Area Number |
13670157
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Aichi Cancer Center |
|---|
Principal Investigator |
OSADA Hirotaka Aichi Cancer Center Research Institute, Division of Molecular Oncology, Section Head, 分子腫瘍学部, 室長 (30204176)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Takashi Aichi Cancer Center Research Institute, Division of Molecular Oncology, Chief, 分子腫瘍学部, 部長 (50231395)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | hepatoma / TGF-β / Apoptosis / 肝癌 |
|---|
| Research Abstract |
We studied the mechanism of apoptosis induction by TGF-β stimuli for the purpose of applying in the cancer therapy. We established several apoptosis-inducible and -uninducible subclones derived from the single hepatoma cell line, which were partially sensitive to TGF-β stimuli. Our preliminary study using apoptosis-specific cDNA arrays showed that the expression of TNF family members were induced by TGF-β stimuli in the apoptosis-inducible subclones. We studied further the signaling pathways from TGF-β stimuli to apoptosis. After TGF-β stimuli, DNA contents, expression of TNF family, and activation of caspase family were sequentially studied. At first, the G1/G2 arrest was transiently observed, and then the induction of TNF family expression, caspase-8 activation, and apoptosis induction occurred sequentially. We studied the effects of neutralizing antibodies against TNF family members and caspase-8 inhibitor, Z-IETD-FMK against the apoptosis induction, and obtained about 50% inhibition of apoptosis. The NF- κB reporter analysis also showed the activation of NF-κB pathway by TGF-β stimuli. Our studies demonstrated the signaling pathway from TGF-β to apoptosis through TNF family induction and caspase-8 activation. Furhter studies using high-density cDNA array may be required to reveal the whole pathways of apoptosis induction. The activation of NF-κB might be associated with the TGF-β -resistance, but it remains to be determined.
|
