title: Cell-cycle distribution and Thymidilate Synthatase (TS) expression correlate with 5-FU resistance in head and neck carcinoma cells.
abstract: BACKGROUND
  Acquired chemoresistance to 5-fluorouracil (5-FU) remains one of the obstacles for the success of 5-FU-based cancer chemotherapy, and some molecular mechanisms of acquired 5-FU resistance are still unknown. The main action of 5-FU is the suppression of DNA replication by inhibiting Thymidylate Synthase (TS).
  
  
  METHODS
  We analyzed 5-FU resistance mechanisms using the head and neck squamous cell carcinoma cell lines, UM-SCC-23, and two different resistant cell lines, UM-SCC-23/WR and UM-SCC-23/MR, which were procured from UM-SCC-23 cells. To acquire resistance, the two cells underwent repeated treatment of 5-FU with different durations and frequency. We determined differences in the cell-cycle distribution and the expression of TS proteins in the three cell lines. Moreover, cell-cycle distribution in cells which acquired resistance after 5-FU treatment, was compared to that of parental cells, using flow cytometric analysis.
  
  
  RESULTS
  There was a remarkable increase in TS protein expression levels in UM-SCC-23/WR following 5-FU treatment. S-phase cells of UM-SCC-23 and UM-SCC-23/WR cells were immediately increased after treatment with 5-FU, whereas UM-SCC-23/MR were accumulated to the S-phase slightly later.
  
  
  CONCLUSIONS
  The cell-cycle perturbation or elevation of TS protein expression may be involved in acquired 5-FU resistance and identifies 5-FU resistance mechanisms in the two different 5-FU treatment regimens.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan ijichi@med.nagoya-cu.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Ijichi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Asahi University Murakami Memorial Hospital, Gifu, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Department of Otorhinolaryngology, Aichi Medical University, Nagakute, Aichi, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D013940:Thymidylate Synthase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil
keywords: 5-FU; cell cycle; head and neck carcinoma; resistance; thymidylate synthase