title: Potential therapeutic benefit of combining gefitinib and tamoxifen for treating advanced lung adenocarcinoma.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of estrogen and estrogen receptor α or β (ERα/β) promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen.
  
  
  METHODS
  We assessed the association between EGFR mutations as well as ERα/β expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells) and A549 (EGFR wild type; Gefitinib-resistant cells) cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen.
  
  
  RESULTS
  We found that the cytosolic but not the nuclear expression of ERβ was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERβ. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib.
  
  
  CONCLUSIONS
  Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERβ in cytosol.
authors.affiliation: Sex Hormone Research Center, Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, 6 Xueshi Rd., North District, Taichung 40403, Taiwan ; Department of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
authors.forename: Chien-Ming
authors.identifier: 0000-0002-1532-9576
authors.initials: CM
authors.lastname: Liu
authors.affiliation: Department of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
authors.forename: Kuo-Liang
authors.initials: KL
authors.lastname: Chiu
authors.affiliation: Department of Pathology, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
authors.forename: Tzu-Sheng
authors.initials: TS
authors.lastname: Chen
authors.affiliation: Department of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
authors.forename: Shang-Miao
authors.initials: SM
authors.lastname: Chang
authors.affiliation: Sex Hormone Research Center, Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, 6 Xueshi Rd., North District, Taichung 40403, Taiwan.
authors.forename: Shu-Yun
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Department of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
authors.forename: Li-Hsiou
authors.initials: LH
authors.lastname: Chen
authors.affiliation: Department of Chest Medicine, Taichung Tzuchi Hospital, The Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
authors.forename: Yung-Lun
authors.initials: YL
authors.lastname: Ni
authors.affiliation: Center of Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yuh-Pyng
authors.identifier: 0000-0002-6062-7556
authors.initials: YP
authors.lastname: Sher
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sung-Liang
authors.identifier: 0000-0003-4535-9036
authors.initials: SL
authors.lastname: Yu
authors.affiliation: Sex Hormone Research Center, Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, 6 Xueshi Rd., North District, Taichung 40403, Taiwan.
authors.forename: Wen-Lung
authors.identifier: 0000-0002-5571-3302
authors.initials: WL
authors.lastname: Ma
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000008:administration & dosage; D013629:Tamoxifen / Q000008:administration & dosage
chemical_list: C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011799:Quinazolines; D013629:Tamoxifen; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib