title: Proteomics finding heat shock protein 27 as a biomarker for resistance of pancreatic cancer cells to gemcitabine.
abstract: Pancreatic cancer remains a devastating disease and >96% of patients with pancreatic cancer do not survive for more than 5 years. Gemcitabine (2'-deoxy-2'-difluoro-deoxycytidine: Gemzar) appears to be the only clinically effective drug for pancreatic cancer, but it has little impact on outcome. Proteomic analysis of gemcitabine-sensitive cells (KLM1) and resistant pancreatic cells (KLM1-R) was performed to identify target proteins of the gemcitabine. We found seven proteins, HSP27, peroxiredoxin 2, endoplasmic reticulum protein ERp29 precursor, 6-phosphogluconolactonase, triosphospate isomerase, alpha enolase, and nucleophosmine that could play a role in determining the sensitivity of pancreatic cancer to gemcitabine. We knocked down HSP27 in KLM1-R and the sensitivity to gemcitabine was restored. In addition, increased HSP27 expression in tumor specimens was related to higher resistibility to gemcitabine in patients of pancreatic cancer. HSP27 may play an important role in the resistibility to gemcitabine, and it could also be a possible biomarker for predicting the response of pancreatic cancer patients to treatment with gemcitabine.
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mori-Iwamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuramitsu
authors.forename: Shomei
authors.initials: S
authors.lastname: Ryozawa
authors.forename: Kuniko
authors.initials: K
authors.lastname: Mikuria
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Maehara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Maehara
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000032:analysis*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D040901:Proteomics; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D003841:Deoxycytidine; D000093542:Gemcitabine