1999 Fiscal Year Final Research Report Summary
Inhibition of apoptosis by tumor-associated serpin, sec antigen-1
| Project/Area Number |
10671547
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
SUMINAMI Yoshinori Yamaguchi University, Hospital, Assistant Professor, 医学部・附属病院, 講師 (50253141)
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| Co-Investigator(Kenkyū-buntansha) |
NAWATA Shugo Yamaguchi University, School of medicine, Assistant, 医学部, 助手 (60294625)
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| Project Period (FY) |
1998 – 1999
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| Keywords | SCC antigen-1 / SCC antigen-2 / apoptosis / serpin / two-hybrid |
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| Research Abstract |
We have shown that transduced tumor cells with SCC Ag-a cDNA is resistant to apoptosis induced by anticancer drug, UV, TNFa, or NK cells. In the present study, we indicated SCC Ag-2 which is highly homologous to SCC Ag-1, is also has an resistant effect to the apoptosis induced by anticancer drug, or radiation. We further investigated the effect of SCC Ag-1 to the molecules which involved in the signalling of the apoptosis. Anticancer drug induced apoptosis indicated the enhanced expression of Bc12 by the existence of SCC Ag-1, while the expression of caspase-2 and caspase-8 was not changed. On the otherhand, the change of expression of Bc12 was not indicated by the existence of SCC Ag-1 when the apoptosis was induced by radiation. These data indicated that SCC Ag-1 has an effect on the upstream of Bc12 in the regulation of apoptosis.
Next we tried to detect the target molecule of SCC Ag-1 and SCC Ag-2 using the yeast two hybrid system. The coding region of SCC Ag-1 or SCC Ag-2 cDNA was cloned in the GAL4 DNA binding domain plasmid (pAS2-1) and sequenced to confirm the direction of insert (pAS2-SCCA1, pAS2-SCCA2). These plasmid was transfected to the yeast with cDNA library of human keratinocyte. However positive signal was not obtained. This is probably due to the large size of the SCC Ag molecule to enter the nucleus. Now we made deleted clones of pAS2-SCCA1 and pAS2-SCCA2 (pAS2-SCCA1 delta, pAS2-SCCA2 delta) which coded SCC Ag about 100 a.a short in N-terminal region to perform further investigation.
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