2003 Fiscal Year Annual Research Report

がん細胞の酸素・栄養飢抵抗性の機構とその進展における役割

Research Project

Project/Area Number	12213153
Research Institution	National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
Principal Investigator	江角浩安国立がんセンター研究所, 支所, 支所長 (70160364)
Keywords	栄養飢餓耐性 / AMPK / Akt / ARK5 / ATM / MT1-MMP / 転移性 / 浸潤転移性
Research Abstract	がん細胞の栄養飢餓耐性にAMPK、Aktが関与していることを明らかにしてきたが、この二つのシグナル伝達系つなぐ分子である、AKTにより燐酸化を受けるARK5を見出してきた.この分子を活性化すると、プロカスパーゼ6の燐酸化をし、その活性化を抑制することにより、アポトーシスを抑制することが分かった。また、MT1-MMPの翻訳レベルの発現誘導を起こし、浸潤転移性が促進されるが、ヒトの大腸がんの臨床検体での検討でも、高発現ががんの進展と関連があることが分かった。一方、細胞を栄養飢餓状態にすると、極めて早い時間に、p53のSer15の燐酸化が起こることが分かったが、この反応には、ARK5-ATM分子のシグナルが関与すうことが分かった。DNA損傷を伴わないATMの活性化は、ATM-p53シグナルの広い範囲の細胞のストレス反応への関与を意味する。ATの多様な病態を理解する上で重要であると同時に、細胞のストレス適応反応を解析する上で重要である。

Research Products

(10 results)

All Other

All Publications (10 results)

[Publications] Kato S., Esumi H., et al.: "Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in human brain tumors : relationships of iNOS to superoxide dismutase (SOD) proteins (SOD1 and SOD2), Ki-67 antigen (MIB-1) and p53 protein."Acta Neuropathol. 105. 333-340 (2003)
[Publications] Kimura H., Esumi H., et al.: "Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis."Acta Biochimica Polonica. 50. 49-59 (2003)
[Publications] Xiong HQ., Esumi H., et al.: "Report of the 16^<th> International Symposium of the Foundation for Promotion of Cancer Research : Recent Advances in Pancreatic Cancer."Jpn J Clin Oncol. 33. 246-253 (2003)
[Publications] Suzuki, A., Esumi H, et al.: "ARKS suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but not by chemotherapeutic agents or UV irradiation."Oncogene. 22. 6177-6182 (2003)
[Publications] Tatemichi M., Esumi H., et al.: "Inducible nitric oxide synthase activity induced by sodium chloride solution prolongs luminal pH elevation in rat and mouse stomachs."J Gastroenterol Hepatol. 18. 1039-1046 (2002)
[Publications] Suzuki A., Esumi H., et al.: "Induction of cell-cell detachment during glucose starvation through F-actin conversion by SNARK, the fourth member of the AMP-activated protein kinase catalytic subunit family."Biochem Biophys Res Commun. 311. 156-161 (2003)
[Publications] Tatemichi M., Esumi H., et al.: "Roles of Inducible Nitric Oxide Synthase in the Development and Healing of Experimentally Induced Gastric Ulcers."Int J Exp Pathol. 84. 213-220 (2003)
[Publications] Suzuki A., Esumi H., et al.: "ARK5 is the Tumor Invasion-Associated Factor Mediating Akt Signaling."Mol Cell Biol. 24. 3526-3535 (2004)
[Publications] Kusakai G., Esumi H., et al.: "ARK5 Expression in Colorectal Cancer and Its Implications for Tumor Progression."Am J Pathol. 164. 987-995 (2004)
[Publications] Kusakai G., Esumi H., et al.: "Involvement of ARK5 in Tumor Invasion and Metastasis."Journal of Experimental and Clinical Cancer Research. (in press).

2003 Fiscal Year Annual Research Report

がん細胞の酸素・栄養飢抵抗性の機構とその進展における役割

Principal Investigator

江角 浩安 国立がんセンター研究所, 支所, 支所長 (70160364)

Research Products

[Publications] Kato S., Esumi H., et al.: "Immunohistochemical expression of inducible nitric oxide synthase (iNOS) in human brain tumors : relationships of iNOS to superoxide dismutase (SOD) proteins (SOD1 and SOD2), Ki-67 antigen (MIB-1) and p53 protein."Acta Neuropathol. 105. 333-340 (2003)

[Publications] Kimura H., Esumi H., et al.: "Reciprocal regulation between nitric oxide and vascular endothelial growth factor in angiogenesis."Acta Biochimica Polonica. 50. 49-59 (2003)

[Publications] Xiong HQ., Esumi H., et al.: "Report of the 16^<th> International Symposium of the Foundation for Promotion of Cancer Research : Recent Advances in Pancreatic Cancer."Jpn J Clin Oncol. 33. 246-253 (2003)

[Publications] Suzuki, A., Esumi H, et al.: "ARKS suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but not by chemotherapeutic agents or UV irradiation."Oncogene. 22. 6177-6182 (2003)

[Publications] Tatemichi M., Esumi H., et al.: "Inducible nitric oxide synthase activity induced by sodium chloride solution prolongs luminal pH elevation in rat and mouse stomachs."J Gastroenterol Hepatol. 18. 1039-1046 (2002)

[Publications] Suzuki A., Esumi H., et al.: "Induction of cell-cell detachment during glucose starvation through F-actin conversion by SNARK, the fourth member of the AMP-activated protein kinase catalytic subunit family."Biochem Biophys Res Commun. 311. 156-161 (2003)

[Publications] Tatemichi M., Esumi H., et al.: "Roles of Inducible Nitric Oxide Synthase in the Development and Healing of Experimentally Induced Gastric Ulcers."Int J Exp Pathol. 84. 213-220 (2003)

[Publications] Suzuki A., Esumi H., et al.: "ARK5 is the Tumor Invasion-Associated Factor Mediating Akt Signaling."Mol Cell Biol. 24. 3526-3535 (2004)

[Publications] Kusakai G., Esumi H., et al.: "ARK5 Expression in Colorectal Cancer and Its Implications for Tumor Progression."Am J Pathol. 164. 987-995 (2004)

[Publications] Kusakai G., Esumi H., et al.: "Involvement of ARK5 in Tumor Invasion and Metastasis."Journal of Experimental and Clinical Cancer Research. (in press).

江角浩安国立がんセンター研究所, 支所, 支所長 (70160364)