Studies on the molecular mechanism of 5-fluorouracil response proteins using a proteomic approach

• Project/Area Number: 23510267
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Living organism molecular science
• Research Institution: Osaka Medical College
• Principal Investigator: SAKAI Akiko 大阪医科大学, 医学部, 講師 (30225750)
• Co-Investigator(Kenkyū-buntansha): TANAKA Satoru 大阪医科大学, 医学部, 助教 (50595741)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 抗癌剤耐性 / プロテオミクス / HSPB1 / オリゴマー化 / サイトケラチン / リン酸化 / 耐性獲得マーカー / 翻訳後修飾 / オリゴマー構造

Outline of Final Research Achievements

The heat-shock protein (HSP) B1 expression increased with the acquisition of 5-fluorouracil resistance. We analyzed the phosphorylation and oligomeric structure of HSPB1 by one- and two-dimensional western blotting via isoelectric focusing and blue native polyacrylamide gel electrophoresis. The oligomeric structures of HSPB1 in resistant cells differed in molecular mass from those in sensitive cells, suggesting that drug resistance alters the phosphorylation and dissociability of HSPB1 oligomers. Further, cytokeratin 8, 18, 19 were identified the proteins that interact with HSPB1 by co-immunoprecipitation.

Research Products

• [Journal Article] Phase II Study of Neoadjuvant Anthracycline-Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer. (2015)
  • Author(s): Tanaka S, Iwamoto M, Kimura K, Matsunami N, Morishima H, Yoshidome K, Nomura T, Morimoto T, Yamamoto D, Tsubota Y, Kobayashi T, Uchiyama K.
  • Journal Title: Clin Breast Cancer Volume: 15 Issue: 3 Pages: 191-196
  • DOI: 10.1016/j.clbc.2014.12.003
  • Peer Reviewed / Open Access
• [Journal Article] Down-regulation of collagen I biosynthesis in intestinal epithelial cells exposed to indomethacin: a comparative proteome analysis. (2014)
  • Author(s): Edogawa S, Sakai A et al
  • Journal Title: Journal of Proteomics Volume: 103 Pages: 35-46
  • DOI: 10.1016/j.jprot.2014.03.022
  • Peer Reviewed
• [Journal Article] Breast conserving surgery using volume replacement with oxidized regenerated cellulose: a cosmetic outcome analysis (2014)
  • Author(s): Tanaka S, Sato N, Fujioka H, Takahashi Y, Kimura K, Iwamoto M, Uchiyama K.
  • Journal Title: Breast J Volume: 20 Pages: 154-158
  • Peer Reviewed
• [Journal Article] Safety of nanoparticle albumin-bound paclitaxel administered to breast cancer patients with clinical contraindications to paclitaxel or docetaxel: Four case reports. (2013)
  • Author(s): Kimura K, Tanaka S et al
  • Journal Title: Oncol Lett. Volume: 6 Issue: 4 Pages: 881-884
  • DOI: 10.3892/ol.2013.1471
  • Peer Reviewed
• [Journal Article] [18F]FDG uptake in proximal muscles assessed by PET/CT reflects both global and local muscular inflammation and provides useful information in the management of patients with polymyositis/dermatomyositis. (2013)
  • Author(s): Tanaka S et al
  • Journal Title: Rheumatology Volume: 52 Issue: 7 Pages: 1271-1278
  • DOI: 10.1093/rheumatology/ket112
  • Peer Reviewed
• [Journal Article] Identification of phosphorylated serine-15 and -82 residues of HSPB1 in 5-fluorouracil-resistant colorectal cancer cells by proteomics. (2012)
  • Author(s): Sakai A, Otani M, Miyamoto A, Yoshida H, Furuya E, Tanigawa N.
  • Journal Title: Journal of Proteomics Volume: 75 Issue: 3 Pages: 806-818
  • DOI: 10.1016/j.jprot.2011.09.023
  • Peer Reviewed
• [Journal Article] Identification of DNA mismatch recognition proteins in the thermophilic bacterium Geobacillus stearothermophilus. (2012)
  • Author(s): Matsunaga F, Sakai A, Mochizuki S, Minami K, Inatsu S.
  • Journal Title: Bulletin of Toyo College of Food Technology Volume: 1 Pages: 9-15
  • NAID: 40019606330
• [Journal Article] YqjD is an inner membrane protein associated with stationary-phase ribosomes in Escherichia coli. (2012)
  • Author(s): Hideji Yoshida, Yasushi Maki, Shou Furuike , Akiko Sakai, Masami Ueta, Akira Wada.
  • Journal Title: J Bacteriol. Volume: 194 Issue: 16 Pages: 4173-4183
  • DOI: 10.1128/jb.00396-12
  • Peer Reviewed
• [Journal Article] Use of contrast-enhanced computed tomography in clinical staging of asymptomatic breast cancer patients to detect asymptomatic distant metastases. (2012)
  • Author(s): Tanaka S, et al
  • Journal Title: Oncol Lett. Volume: 3 Pages: 772-776
  • Peer Reviewed
• [Journal Article] A case of solitary breast metastasis from malignant melanoma of the nasal cavity. (2012)
  • Author(s): Tanaka S, et al
  • Journal Title: Oncol Lett. Volume: 4 Pages: 889-892
  • Peer Reviewed
• [Journal Article] Association between body mass index and breast cancer intrinsic subtypes in Japanese women. (2012)
  • Author(s): Kimura K, Tanaka s, et al
  • Journal Title: Exp Ther Med. Volume: 4 Pages: 391-396
  • Peer Reviewed
• [Journal Article] Phosphoproteome profiling using a fluorescent phosphosensor dye in two-dimensional polyacrylamide gel electrophoresis. (2011)
  • Author(s): Otani M, Taniguchi T, Sakai A, et al.
  • Journal Title: Appl Biochem Biotechnol Volume: 164 Issue: 6 Pages: 804-818
  • DOI: 10.1007/s12010-011-9175-5
  • Peer Reviewed
• [Journal Article] Esthetic result of rhomboid flap repair after breast-conserving surgery for lower quadrant breast cancer lesion with skin invasion: report of two cases. (2011)
  • Author(s): Tanaka S, et al
  • Journal Title: Surg. Today Volume: 41 Issue: 6 Pages: 832-836
  • DOI: 10.1007/s00595-010-4355-4
  • NAID: 10029048170
  • Peer Reviewed
• [Presentation] 抗癌剤耐性株における熱ショック蛋白質HSPB1の翻訳後修飾とオリゴマー構造 (2014)
  • Author(s): 境晶子，林秀行
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 抗癌剤5-FU耐性株におけるHSPB1のリン酸化とオリゴマー構造 (2011)
  • Author(s): 境 晶子
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜国際会議場