2004 Fiscal Year Final Research Report Summary
Investigation on the role of SOCS family in the development of lung cancer. and its application to cancer therapy
| Project/Area Number |
15590809
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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 |
Respiratory organ internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
OSAKI Tadashi Osaka University, Graduate School of Medicine, assistant professor, 医学系研究科, 助手 (50324778)
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| Co-Investigator(Kenkyū-buntansha) |
KARASE Ichiro Osaka University, Graduate School of Medicine, professor, 医学系研究科, 教授 (10161324)
NAKA Tetsuji Osaka University, Graduate School of Medicine, assistant professor, 医学系研究科, 助手 (30303936)
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| Project Period (FY) |
2003 – 2004
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| Keywords | STAT / SOCS / PIAS / lung cancer / cell growth / chemosensitivity / suppressor of cancer |
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| Research Abstract |
The Janus kinase-signal transducers and activators of transcription (Jak-STAT) pathway is known to mediate signals from growth factors and cytokines. It is also closely related to development of cancer as shown in hepatocellular carcinoma cells. In this study, we showed that not only inactivation of suppressor of cytokine signaling (SOCS) but also protein inhibitor of activated STAT (PIAS), have inhibitory effects on development of lung cancer cells mediating the Jak-STAT pathway. We established transfectants of PIAS3 in A549, a lung cancer cell line and MT37, a malignant mesothelioma cell line in order to block signals mediating Jak-STAT pathway. In these PIAS3 transfectants, phosphorylation of STAT3 induced by interleukin 6 was completely inhibited. Cell growth in vitro of the PIAS3 transfectants was significantly retarded as compared to that of wild-type cells. Expression of SOCS3 also inhibited growth of the A549 cells. Transduction of PIAS3 rendered A549 cells 5 times sensitive to carboplatin. These results are partly explained by findings that PIAS3 transfectants tend to be apoptotic when exposed to carboplatin at a high concentration. In conclusion, we show that both SOCS and PIAS possess inhibitory effects on development of lung cancer cells.
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