2002 Fiscal Year Annual Research Report

口腔癌の微小転移機構の解析と分子標的治療による転移阻止

Research Project

Project/Area Number	14207091
Research Institution	Ehime University
Principal Investigator	浜川裕之愛媛大学, 医学部, 教授 (20127905)
Co-Investigator(Kenkyū-buntansha)	中城公一愛媛大学, 医学部附属病院, 講師 (90314880) 新谷悟愛媛大学, 医学部, 助教授 (80294429)
Keywords	口腔癌 / 浸潤 / 転移 / GFP / マイクロアレイ
Research Abstract	平成14年度は口腔癌頸部リンパ節高転移株にGreen fluorescent Protein(GFP)遺伝子を安定発現させ、可視化した細胞で、その転移機構を解析することを試みた。保有しているGFP-SAS-T5、GFP-SAS-L1、GFP-BSCCの3株に加え、ACC-2と、ACC-2から樹立され高頻度に遠隔転移を起こすACC-MにGFPを安定発現させることで、GFP-ACC2ならびにGFP-ACC-Mの2株を新たに樹立した。また、舌への同所性移植、頸部リンパ節転移モデルを用い、扁平上皮癌細胞株HSC2、HSC3、HSC4の頸部リンパ節への転移率を検討したところ、同所性移植は全例生着するものの、HSC2で30%、HSC3で80%、HSC4で20%と異なった頸部リンパ節転移率を示した。つぎに、腺様嚢胞癌親株ACC-2とその高転移株ACC-Mとに対しcDNAマイクロアレイの発現パターンを比較検討した。各細胞株からmRNAを抽出し、これをReverse transcriptionしcDNAとし、これをマイクロアレイにより解析した。GMS418 Array Scannerを用い、IntelliGene^<TM> DNA CHIPを使用した。その結果、親株ACC-2で発現亢進した遺伝子としては細胞周期関連としてp53,RB2/p130,cyclin G1,修復酵素のhMSH2,接着分子ではbeta-catenin, desmoplakin 1, Integrin beta1, APCなどであった。一方、高転移性株ACC-Mは蛋白分解酵素であるMMP-2,MMP-16、アポトーシス関連ではapoptosis inhibitor survivin, bcl-2,細胞周期関連ではmdm2, PCNA, cdc25Aなどが発現亢進していた。このことから、高転移性のphenotypeを示すACC-Mは細胞周期を促進し、アポトーシスを回避する機構さらには接着分子の不安定化を生じ、浸潤、転移能の亢進を遺伝子レベルの分子機構で獲得していることが確認された。

Research Products

(10 results)

All Other

All Publications (10 results)

[Publications] Begum NM, Nakashiro K, Kawamata H, Uchida D, Shintani S, Ikawa Y, Sato M, Hamakawa H: "Expression of peroxisome proliferator-activated receptor gamma and the growth inhibitory effect of its synthetic ligands in human salivary gland cancer cell lines"Int J Oncol. 20(3). 599-605 (2002)
[Publications] S.Shintani, M.Mihara, Y.Nakahara, T.Aida, T.Tachikawa, H.Hamakawa: "Lymph node metastasis of oral cancer visualised in live tissue by green fluorescent protein expression"Oral Oncology. 38(7). 664-669 (2002)
[Publications] Li C, Shintani S.Terakado N, Nakashiro K, Hamakawa H: "Infiltration of tumor-associated macrophages in human oral squamous cell carcinoma"Oncol Rep. 9. 1219-1223 (2002)
[Publications] M.Mihara, S.Shintani, K.Nakashiro, H.Hamakawa: "Flavopiridol, a cyclin dependent kinase (CDK) inhibitor, induces apoptosis by regulating Bcl-x in oral cancer cells"Oral Oncology. 39(1). 49-55 (2003)
[Publications] Kiyota A, Shintani S, Mihara M, Nakahara Y, Ueyama U, Matsumura T, Tachikawa T, Wong DT W.: "Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27KIP1 and p15INK4B, and induces G1 arrest in oral squamous carcinoma cell lines"Oncology. 63. 92-98 (2002)
[Publications] Mihara M, Shintani S, Kiyota A, Matsumura T, Wong DT W.: "Cyclin-dependent kinase inhibitor (Roscovitine) suppresses the growth and induce apoptosis by regulating Bcl-x in head and neck squamous cell carcinoma cells"Int J Oncol. 21. 95-101 (2002)
[Publications] Omotehara F, Kawamata H, Uchida D, Hino S, Nakashiro K, Fujimori T.: "Vesnarinone, a differentiation inducing drug, directly activates p21(waf1)gene promoter via Sp1 sites in a human salivary gland cancer cell line"Br J Cancer. 87. 1042-1046 (2002)
[Publications] Hoque MO, Kawamata H, Nakashiro K, Omotehara F, Hino S, Uchida D, Harada K, Begum NM, Yoshida H, Sato M, Fujimori T.: "Dysfunction of the p53 tumor suppressor pathway in head and neck cancer"Int J Oncol. 21. 119-126 (2002)
[Publications] Shinagawa Y, Kawamata H, Omotehara F, Nakashiro K, Hoque MO, Furihata T, Horiuchi H, Imai Y, Fujimori T, Fujibayashi T.: "Evaluation of the chemosensitivity of head and neck cancer cells based on the diverse function of mutated-p53"Int J Oncol. 22. 383-389 (2003)
[Publications] Shintani S, Kiyota A, Mihara M, Sumida T, Kayahara H, Nakashiro K, Hamakawa H.: "Enhancement of radiosensitivity in head and neck cancer cells by ZD1839 ('Iressa'), a selective epidermal growth factor receptor tyrosine kinase inhibitor"Am J Clin Oncol. (In press). (2003)

2002 Fiscal Year Annual Research Report

口腔癌の微小転移機構の解析と分子標的治療による転移阻止

Principal Investigator

浜川 裕之 愛媛大学, 医学部, 教授 (20127905)

Research Products

[Publications] Begum NM, Nakashiro K, Kawamata H, Uchida D, Shintani S, Ikawa Y, Sato M, Hamakawa H: "Expression of peroxisome proliferator-activated receptor gamma and the growth inhibitory effect of its synthetic ligands in human salivary gland cancer cell lines"Int J Oncol. 20(3). 599-605 (2002)

[Publications] S.Shintani, M.Mihara, Y.Nakahara, T.Aida, T.Tachikawa, H.Hamakawa: "Lymph node metastasis of oral cancer visualised in live tissue by green fluorescent protein expression"Oral Oncology. 38(7). 664-669 (2002)

[Publications] Li C, Shintani S.Terakado N, Nakashiro K, Hamakawa H: "Infiltration of tumor-associated macrophages in human oral squamous cell carcinoma"Oncol Rep. 9. 1219-1223 (2002)

[Publications] M.Mihara, S.Shintani, K.Nakashiro, H.Hamakawa: "Flavopiridol, a cyclin dependent kinase (CDK) inhibitor, induces apoptosis by regulating Bcl-x in oral cancer cells"Oral Oncology. 39(1). 49-55 (2003)

[Publications] Kiyota A, Shintani S, Mihara M, Nakahara Y, Ueyama U, Matsumura T, Tachikawa T, Wong DT W.: "Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27KIP1 and p15INK4B, and induces G1 arrest in oral squamous carcinoma cell lines"Oncology. 63. 92-98 (2002)

[Publications] Mihara M, Shintani S, Kiyota A, Matsumura T, Wong DT W.: "Cyclin-dependent kinase inhibitor (Roscovitine) suppresses the growth and induce apoptosis by regulating Bcl-x in head and neck squamous cell carcinoma cells"Int J Oncol. 21. 95-101 (2002)

[Publications] Omotehara F, Kawamata H, Uchida D, Hino S, Nakashiro K, Fujimori T.: "Vesnarinone, a differentiation inducing drug, directly activates p21(waf1)gene promoter via Sp1 sites in a human salivary gland cancer cell line"Br J Cancer. 87. 1042-1046 (2002)

[Publications] Hoque MO, Kawamata H, Nakashiro K, Omotehara F, Hino S, Uchida D, Harada K, Begum NM, Yoshida H, Sato M, Fujimori T.: "Dysfunction of the p53 tumor suppressor pathway in head and neck cancer"Int J Oncol. 21. 119-126 (2002)

[Publications] Shinagawa Y, Kawamata H, Omotehara F, Nakashiro K, Hoque MO, Furihata T, Horiuchi H, Imai Y, Fujimori T, Fujibayashi T.: "Evaluation of the chemosensitivity of head and neck cancer cells based on the diverse function of mutated-p53"Int J Oncol. 22. 383-389 (2003)

[Publications] Shintani S, Kiyota A, Mihara M, Sumida T, Kayahara H, Nakashiro K, Hamakawa H.: "Enhancement of radiosensitivity in head and neck cancer cells by ZD1839 ('Iressa'), a selective epidermal growth factor receptor tyrosine kinase inhibitor"Am J Clin Oncol. (In press). (2003)

浜川裕之愛媛大学, 医学部, 教授 (20127905)