2004 Fiscal Year Final Research Report Summary
Functional analyses of novel tumor suppressor genes by gene targeting
| Project/Area Number |
15590335
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Shiga University of Medical Science |
|---|
Principal Investigator |
INOUE Hirokazu School of Medicine, Department of Microbiology, Associate Professor, 医学部, 助教授 (30176440)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HARAGUCHI Seiki School of Medicine, Department of Microbiology, Research Associate, 医学部, 助手 (10324576)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Tumor suppressor gene / Apoptosis / Knockout mouse / Drs |
|---|
| Research Abstract |
The drs gene was originally isolated as a suppressor against v-src transformation.
Drs protein has one transmembrane domain and three consensus repeat called Sushi motif. Expression of drs mRNA was markedly downregulated in a variety of human cancer cell lines and tissues, suggesting that the drs gene acts as a tumor suppressor. In this study, we investigated the function of Drs and the mechanism of tumor suppression by this gene and obtained the following results.
(1)Drs induces apoptosis by a novel pathway mediated by ASY/Nogo-B/RTN-xS, caspase-12, caspase-9 and caspase-3 in human cancer cells.
(2)We investigated the tumor suppressor function in vivo of drs and its physiological roles in apoptosis by generating a gene-knockout mouse. Malignant tumors including lymphomas, lung adenocarcinomas, hepatomas, and sarcoma were generated in about 25% of 46 drs-knockout(KO)mice. No tumors were detected in all (23) wild-type mice examined at the same age.
(3)Re-introduction of drs by retrovirus vector into a lung cancer cell line derived from a lung adenocarcinoma of a drs KO mouse caused suppression of tumorigenicity in nude mouse and elevation of apoptosis mediated by activation of caspase-3.
(4)Drs KO MEF cells showed resistance to certain apoptosis-inducing reagent such as rapamycine and dexamethazone.
(5)Apoptosis was induced in glucose-depleted Drs KO MEF cells, suggesting the closstalk between Drs-induced apoptosis pathway and mTOR signal pathway.
These results idicate that the drs gene acts as a tumor suppressor in genesis of malignant tumors and that drs play a role in certain apoptotic pathways in physiological conditions.
|
Research Products
(21 results)
-
-
-
-
-
[Journal Article] A novel apoptotic pathway induced by the drs tumor suppressor gene.2004
Author(s)
Tambe, Y., Isono, T..Haraguchi, S., Yoshioka-Yamashita, A, Yutsudo, M.,, Inoue.H.
-
Journal Title
Oncogene 23
Pages: 2977-2987
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Loss of c-abl facilitates anchorage-independent growth of p53-and RB-deficient primary mouse embryonic fibroblasts.2004
Author(s)
Suzuki, J., Sukezane, T., Akagi, T., Georgescu, M.M., Ohtani, M., Inoue, H., Jat, P.S., Goff, S.P., Hanafusa, H., Shishido, Y.
-
Journal Title
Oncogene 23
Pages: 8527-8534
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
-
-
[Journal Article] Pro-apoptotic ASY/Nogo-B protein associates with ASYIP.2003
Author(s)
Qi, B., Qi, Y., Watari, A., Yoshioka, N., Inoue, H., Minemoto, Y., Yamashita, K., Sasagawa, T., Yutsudo, M.
-
Journal Title
J.Cell.Physiol. 196
Pages: 312-318
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Down-regulation of drs mRNA in human prostate carcinomas.2003
Author(s)
Kim, C.J., Shimakage, M., Kushima, R., Mukaisho, K., Shinka, T., Okada, Y., Inoue.H.
-
Journal Title
Human Pathology 34
Pages: 654-657
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Expression of Epstein-Barr virus in thyroid carcinoma correlates with tumor progression.2003
Author(s)
Shimakage, M., Kawahara, K., Sasagawa, T., Inoue, H., Yutsudo, M., Yoshida, M., Yanoma, S.
-
Journal Title
Human Pathology 34
Pages: 1170-1177
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Conserved role of nanos proteins in germ cell development.2003
Author(s)
Tsuda, M., Sasaoka, Y., Kiso, M., Abe, K., Haraguchi, S., Kobayashi, S., Saga, Y.
-
Journal Title
Science 301
Pages: 1239-1241
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] nanos1 : a mouse nanos gene expressed in the central nervous system is dispensable for normal development.2003
Author(s)
Haraguchi, S., Tsuda, M., Kitajima, S., Sasaoka, Y, Nomura-Kitabayashid, A., Kurokawa, K., Saga, Y.
-
Journal Title
Mech.Dev. 120
Pages: 721-731
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] Rb1cc1 is critical for myoblast differentiation through Rb1 regulation.
Author(s)
Watanabe, R., Chano, T., Inoue, H., Isono, T., Koiwai, O., Okabe, H.
-
Journal Title
Virchows Arch. 446(in press)
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Periostin is down-regulated in high grade human bladder cancers and suppresses in vitro cell invasiveness and in vivo metastasis of cancer cells.
Author(s)
Kim, C.J., Yoshioka, N., Tambe, Y., Kushima, R., Okada, Y., Inoue, H.
-
Journal Title
Description
「研究成果報告書概要(欧文)」より
-
