Analysis of cisplatin resistance of PTP4A1 and identification of new endogenous resistance gene to cisplatin

• Project/Area Number: 25462912
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hokkaido University
• Principal Investigator: Kitamura Tetsuya 北海道大学, 歯学研究科, 助教 (00451451)
• Co-Investigator(Kenkyū-buntansha): 進藤 正信 北海道大学, 歯学研究科(研究院), 教授 (20162802) ; 東野 史裕 北海道大学, 歯学研究科, 准教授 (50301891) ; 松田 彩 北海道大学, 歯学研究科, 特別研究員(RPD) (60514312)
• Research Collaborator: UEDA Michihiro 北海道がんセンター
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: シスプラチン耐性 / シスプラチン / 抗癌剤 / 内因性耐性遺伝子 / PTP4A1 / 抗癌剤耐性遺伝子

Outline of Final Research Achievements

We have explored cisplatin resistance genes to predict the efficacy of chemotherapy for oral cancer. In this experiments we established resistance and sensitive cell lines. Since PTP4A1 has been identified as resistance gene before by us, we analyzed PTP4A1 mRNA expression in both cell lines. But there was no difference between resistance and sensitive cell lines. We found JNK inhibitor caused cell death especially in resistance cell lines. JNK activity was more increased in resistance cell lines compared to sensitive. These results indicated JNK activity was related to cisplatin resistance and combination of cisplatin and JNK inhibitor can eliminate cancer tissue which have tolerance to cisplatin.

Research Products

• [Journal Article] Expression patterns of ALDH1 and podoplanin predict the risk of malignant transformation in oral leukoplakia. (2017)
  • Author(s): Habiba U, Hida K, Kitamura T, Yanagawa-Matsuda A, Higashino F,Ito YM, Ohiro Y, Totsuka Y, Shindoh M
  • Journal Title: Oncology Letters Volume: 13 Issue: 1 Pages: 321-328
  • DOI: 10.3892/ol.2016.5379
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] HuR and podoplanin expression is correlated with high risk of malignant transformation in patients with oral preneoplastic lesions. (2016)
  • Author(s): Habiba U., Hida K., Higashino F., Kitamura T., Yanagawa-Matsuda A., Totsuka Y. and Shindoh M.
  • Journal Title: Oncology Letters Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Identification of marker genes required to predict oral cancer cells with intrinsic resistance to cisplatin. (2016)
  • Author(s): Kitamura T., Higashino F., Yanagawa-Matsuda A., Ueda M., Kashiwao K., Okada T., Ohiro Y., and Shindoh M.
  • Journal Title: Oncology Letters Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Filamin acts as a key regulator in epithelial defence against transformed cells. (2014)
  • Author(s): Kajita M., Sugimura, K., Ohoka, A., Burden, J., Suganuma, H., Ikegawa, M., Shimada, T., Kitamura, T., Shindoh, M., Ishikawa, S., Yamamoto, S., Saitoh, S., Yako, Y., Takahashi, R., Okajima, T., Kikuta, J., Maijima, Y., Ishii, M., Tada, M., and Fujita, Y.
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 4428-4428
  • DOI: 10.1038/ncomms5428
  • Peer Reviewed / Open Access
• [Journal Article] Cytoplasmic expression of HuR may be a valuable diagnostic tool for determining the potential for malignant transformation of oral verrucous borderline lesions (2014)
  • Author(s): Habiba U., Kitamura T., Yanagawa-Matsuda A., Hida K., Higashino F., Ohiro Y., Totsuka Y. and Shindoh M
  • Journal Title: Oncology Reports Volume: 31 Issue: 4 Pages: 1547-1554
  • DOI: 10.3892/or.2014.3017
  • Peer Reviewed / Open Access
• [Journal Article] pp32r1 controls the decay of the RNA-binding protein HuR (2014)
  • Author(s): Imamachi K., Higashino F., Kitamura T., Kakuguchi W., Yanagawa-Matsuda A., Ishikawa M., Kitagawa Y., Totsuka Y. and Shindoh M
  • Journal Title: Oncology Reports Volume: 31 Issue: 3 Pages: 1103-1108
  • DOI: 10.3892/or.2013.2956
  • NAID: 120005465481
  • Peer Reviewed / Open Access
• [Journal Article] Expression of parathyroid hormone-related protein confers malignant potential to mucoepidermoid carcinoma (2013)
  • Author(s): Nagamine K, KitamuraT
  • Journal Title: Oncol Rep Volume: 29(6) Issue: 6 Pages: 2114-8
  • DOI: 10.3892/or.2013.2393
  • Peer Reviewed
• [Presentation] Predicting the chemo-sensitivity for cisplatin in oral squamous cell carcinoma (2016)
  • Author(s): Tetsuya Kitamura, Keita Kashiwao , Tomoyuki Okada, Aya Yanagana-Matsuda, Michihiro Ueda, Fumihiro Higashino, Masanobu Shindoh
  • Organizer: American Association for Dental Reseach
  • Place of Presentation: Los angeles convention center (Carfornia)
  • Year and Date: 2016-03-16
  • Int'l Joint Research
• [Presentation] mRNA安定化機構を利用した腫瘍溶解アデノウイルス (2015)
  • Author(s): 東野史裕、三河洋平、北村哲也、松田 彩、鄭 朱蒙、進藤正信
  • Organizer: 第74回日本がん学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-10-10
• [Presentation] アデノウイルス感染によるHuRの挙動はウイルス複製と関連する (2015)
  • Author(s): 松田 彩、北村哲也、東野史裕、黒嶋雄志、鄭 朱蒙、ウンマ ハビバ、進藤正信
  • Organizer: 第104回日本病理学会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-05-02
• [Presentation] Identification of intrinsic cisplatin resistance genes (2014)
  • Author(s): Tetsuya Kitamura, Keita Kashiwao , Tomoyuki Okada, Aya Yanagana-Matsuda, Fumihiro Higashino, Masanobu Shindoh
  • Organizer: 92th International Association for Dental Research
  • Place of Presentation: Cape town (South africa)
  • Year and Date: 2014-06-29
• [Presentation] 5型アデノウイルスによるStress granules 形成阻害 (2014)
  • Author(s): 北村哲也、松田彩、東野史裕、進藤正信
  • Organizer: 第68回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-05-09
• [Presentation] アデノウイルスによる宿主細胞のストレス応答機構の制御 (2014)
  • Author(s): 北村哲也、松田彩、鄭朱蒙 パトリック、東野史裕、進藤正信
  • Organizer: 第10３回 日本病理学会
  • Place of Presentation: 広島国際会議場（広島県広島市）
  • Year and Date: 2014-04-25
• [Presentation] 口腔がんにおけるシスプラチン 内因性耐性遺伝子の検索
  • Author(s): 北村 哲也
  • Organizer: 日本口腔科学会
  • Place of Presentation: 栃木県総合文化センター（宇都宮）
• [Presentation] アデノウイルス感染によるStress granules形成阻害
  • Author(s): 北村 哲也
  • Organizer: 臨床口腔病理学会
  • Place of Presentation: 日本大学歯学部（東京都）
• [Presentation] シングルセルクローニング法を応用した シスプラチン内因性耐性遺伝子の同定
  • Author(s): 北村 哲也
  • Organizer: 日本病理学会
  • Place of Presentation: 北海道ロイトンホテル（札幌）
• [Book] 検査と臨床 (2016)
  • Author(s): 北村哲也
  • Total Pages: 3
  • Publisher: 医学書院