title: Antiproliferative effects of gefitinib are associated with suppression of E2F-1 expression and telomerase activity.
abstract: BACKGROUND
  Gefitinib (Iressa, ZD1839) is a selective epidermal growth factor receptor tyrosine kinase inhibitor. E2F-1 is a critical determinant in cell cycle. Growth signals up-regulate telomerase activity. The effects of gefitinib on E2F-1 and telomerase in A549, H23 and A431 cells were examined.
  
  
  METHODS
  Cell proliferation and cell cycle progression were measured by the WST-1 assay and flow cytometry. The expression of E2F-1 and cyclin-dependent kinase inhibitors was evaluated, and hTERT mRNA expression and telomerase activity were analyzed.
  
  
  RESULTS
  In the A431 and A549 cells, treatment with gefitinib inhibited cell proliferation and was associated with an increase in G1-phase. In both cell types, gefitinib decreased the expression of E2F-1 mRNA and protein, followed by the suppression of hTERT mRNA and telomerase activity. In the H23 cells, gefitinib did not affect cell proliferation.
  
  
  CONCLUSIONS
  The antiproliferative effects of gefitinib may be, at least in part, due to the inhibition of E2F-1 expression and telomerase activity.
authors.affiliation: Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima 890-8520, Japan. suenagam@m3.kufm.kagoshima-u.ac.jp
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Suenaga
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Soda
authors.forename: Koji
authors.initials: K
authors.lastname: Orihara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tokito
authors.forename: Yoshimune
authors.initials: Y
authors.lastname: Sakaki
authors.forename: Megumi
authors.initials: M
authors.lastname: Umehara
authors.forename: Kenji
authors.initials: K
authors.lastname: Terashi
authors.forename: Nakaaki
authors.initials: N
authors.lastname: Kawamata
authors.forename: Mikio
authors.initials: M
authors.lastname: Oka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.forename: Chuwa
authors.initials: C
authors.lastname: Tei
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D015536:Down-Regulation; D050687:E2F1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D016193:G1 Phase / Q000187:drug effects*; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014846:Vulvar Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D011799:Quinazolines; D012333:RNA, Messenger; D066246:ErbB Receptors; C509186:TERT protein, human; D019098:Telomerase; D000077156:Gefitinib