RBM5 plays important roles in the post-transcriptional regulation of mRNAs that are involved in the metabolism of chemotherapeutic reagents.

• Project/Area Number: 23591007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: KAWAKAMI Hiroshi 北海道大学, 大学病院, 助教 (80399823)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Takahiko 北海道大学, 大学院医学研究科, 客員研究 員 (80333607)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 薬剤耐性 / 抗癌剤耐性 / 膵癌

Research Abstract

Despite recent advances in various chemotherapeutic regimens, pancreatic cancer remains highly resistant to conventional chemotherapy. The putative tunor suppressor RBM5 is known to modulate apoptosis and cell cycle arrest but the molecular mechanisms of RBM5 function are poorly understood.
We show here that RBM5 interacted with HuR, which is one of mRNA regulatory proteins that bind AU-rich elements in the 3'-untranslated regions of target mRNAs, stabilizing them and modulating their translation. Certain cell stresses including chemotherapeutic reagents induce translocation of HuR from the nucleus to the cytoplasm. RBM5 associated with HuR in the nucleus and reduced translocation of HuR to the cytoplasm. Furthermore, RBM5 overexpression decreased the association of HuR with target mRNAs.
Taken together, we suggest that RBM5 might play important roles in the post-transcriptional regulation of mRNAs that are involved in the metabolism of chemotherapeutic reagents.

Research Products

• [Journal Article] CTNNB1 mutational analysis of solid-pseudopapillary neoplasms of the pancreas using endoscopic ultrasound-guided fine-needle aspiration and next-generation deep sequencing. (2014)
  • Author(s): Kubota Y, Kawakami H, Natsuizaka M, Kawakubo K, Marukawa K, Kudo T, Abe Y, Kubo K, Kuwatani M, Hatanaka Y, Mitsuhashi T, Matsuno Y, Sakamoto N.
  • Journal Title: J Gastroenterol. Volume: in press Issue: 2 Pages: 203-210
  • DOI: 10.1007/s00535-014-0954-y
  • NAID: 120005693897
  • Peer Reviewed
• [Journal Article] Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer. (2013)
  • Author(s): Eto K, Kawakami H, Kuwatani M, Kudo T, Abe Y, Kawahata S, Takasawa A, Fukuoka M, Matsuno Y, Asaka M, Sakamoto N.
  • Journal Title: Br J Cancer Volume: 108 Issue: 7 Pages: 1488-1494
  • DOI: 10.1038/bjc.2013.108
  • NAID: 120005341786
  • Peer Reviewed
• [Journal Article] -FNA for suspected malignant biliary strictures after negative endoscopic transpapillary brush cytology and forceps biopsy (2011)
  • Author(s): Ohshima Y, Yasuda I, Kawakami H, Kuwatani M, Mukai T, Iwashita T, Doi S, Nakashima M, Hirose Y, Asaka M, Moriwaki H.
  • Journal Title: J Gastroenterol Volume: 46(7) Issue: 7 Pages: 921-928
  • DOI: 10.1007/s00535-011-0404-z
  • Peer Reviewed
• [Presentation] 切除不能膵癌に対する超音波内視鏡下穿刺吸引生検検体を用いたgemcitabine感受性予測因子の検討 (2013)
  • Author(s): 江藤和範,河上洋,坂本直哉
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 城山観光ホテル(鹿児島市)
• [Presentation] 切除不能膵癌に対する超音波内視鏡下穿刺吸引生検検体を用いたgemcitabine 感受性予測因子の検討 (2013)
  • Author(s): 江藤和範，河上 洋，坂本直哉
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 城山観光ホテル（鹿児島市）
• [Presentation] 超音波内視鏡下穿刺吸引生検検体を用いた膵癌における抗癌剤感受性予測因子の検討 (2012)
  • Author(s): 江藤和範,河上洋,坂本直哉
  • Organizer: 第43回日本膵臓学会
  • Place of Presentation: ホテルメトロポリタン山形(山形市)
• [Presentation] 超音波内視鏡下穿刺吸引生検検体を用いた膵癌における抗癌剤感受性予測因子の検討 (2012)
  • Author(s): 江藤和範，河上 洋，坂本直哉
  • Organizer: 第43回日本膵臓学会
  • Place of Presentation: ホテルメトロポリタン山形（山形市）