2002 Fiscal Year Final Research Report Summary
Inductioin and activation of p53 tumor suppressor protein by Cdt in HPV-related cancer cells
| Project/Area Number |
13671962
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
病態科学系歯学(含放射線系歯学)
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
YAMATO Kenji Tokyo Medical and Dental University, Graduate School, Division of Oral Health Science, Lecturer, 大学院・医歯学総合研究科, 講師 (50174751)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NISHIHARA Tatsuji Kyushu Dental College, Professor, 歯学部, 教授 (80192251)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Keywords | BPV / p53 / E6 / siRNA / Cdt / P |
|---|
| Research Abstract |
The cytolethal distending toxin (Cdt) from Actinobacillus actinomycetemcomitans has been shown to induce cell cycle arrest in the G2 phase as well as cell death in mammalian cells. However, the precise mechanism by which the toxin induces these effects remains unknown. Human papillomavirus-16 (HPV-16) and HPV-18 are considered as causative agents of most human rectogenital cancers and part of oropharyngeal cancers. The E7 viral oncoprotein inactivates the retinoblastoma-related gene-product (Rb) and the E6 oncoprotein inhibits the p53 tumor suppressor protein by promoting its degradation.
We have found that Cdt caused accumulation of p53 during the induction of G2 arrest and cell death in HPV-18 positive HeLa cells. HS-72 mouse hybridoma cells expressing wild-type p53 were stably transfected with HPV-16 E6/E7. Using E6/E7-expressing HS-72 cells, we demonstrated that these cells were also sensitive to Cdt-mediated G2 arrst and cell death. To explore the molecular mechanism of p53 accumulation, we established the the siRNA system in HPV-positive cancer cell lines (HeLa, SiHa).Using lamin A/C siRNA which had been reported to exhibit a strong RNAi activity, we maximize the induction rate of siRHA into these cells. He found that HeLa cells and SiHa cells can be introduced with siRNA with a extremely high efficiency (more than 90%). We also found synthesized HPV-16 E6 and E7 siRNAs down-regulated the expression E6 and E7 mRHA by 70% and 80%, respectively. These results showed that SiHa cells were highly susceptible to siRNA. We are now planning to study if either ATM, ATR, Chkl, Chk2, DNA-PK or ARF is involved in the Cdt-induced p53 accumulation using the siRNA method.
|
Research Products
(14 results)
-
-
-
-
-
-
-
-
[Publications] Sato, T., Koseki, T., Yamato, K., Saiki, K., Kosishi, K., Yoshikawa, M., ishikawa, I., Nishihara, T.: "p53-independent expression of p21^<CIP1/WAP1> in plasmacytic ceils during G2 cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal distending toxin"Infect. Immun.. 70. 528-534 (2002)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Yamato, K., Hashimoto, s., Imamura, T., Uchida, H., Okahashi, N., Koseki, T., Ishisaki, A., Kizaki, M., Miyazono, K., Ikeda, Y., Nishihara, T.: "Activation of the p21^<CIP1/WAP1> promoter by bone morphogenetic protein-2 in mouse B lineage cells"Oncogene. 20. 4383-4392 (2001)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Koseki, T., Gao, Y., Okahashi, N., Murase, Y., Tsujisawa, T., Sato, T., Yamato, K., Nishihara, T.: "Role of TGF-b family in osteoclastogenesis induced by RANKL"Cell Signal. 14. 31-36 (2002)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Muto, A., Kizaki, M., Kawamura, C., Matsushita, H., Fukuchi, Y., Umezawa, A., Yamada, T., Hata, J., Hozumi, N., Yamato, K., Ito, M., ueyama, Y., Ikeda, Y.: "A novel differentiation-inducing therapy for acute promyelocytic leukemia with a combination of arsenic trioxide and GM-CSF"Leukemia. 15. 528-534 (2001)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Okahashi, N., Murase, Y., Koseki, T., Sato, T., Yamato, K., Nishihara, T.: "steoclast differentiation is associated with transient upregulation of cyclin-dependent kinase inhibitors"J. Cell. Biochem.. 80. 339-345 (2001)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Nakahara, T., Tominaga, K., Koseki, T, Yamamoto, M., Yamato, K., and Nishihara, T.: "Growth/differentiation factor-5 induces growth arrest and apoptosis in mouse B lineage cells with"Cell. Signal.. 15. 181-187 (2003)
Description
「研究成果報告書概要(欧文)」より
-
[Publications] Ito, K., Nakazota, T., Miyakawa, Y., Yamato, K., Ikeda, Y., and Kizaki, M.: "Caffeine induces G2/M arrest and apoptosis via novel p53-dependent pathway in NB4 prdmonocytic leukemia cells"J. Cell Physiol.. in press.
Description
「研究成果報告書概要(欧文)」より
