title: Brachyury, a driver of the epithelial-mesenchymal transition, is overexpressed in human lung tumors: an opportunity for novel interventions against lung cancer.
abstract: OBJECTIVE
  The epithelial-mesenchymal transition (EMT) is emerging as a critical factor for the progression and metastasis of carcinomas, as well as drug resistance. The T-box transcription factor Brachyury has been recently characterized as a driver of EMT in human carcinoma cells. The purpose of this study was to characterize Brachyury as a potential target for lung cancer therapy.
  
  
  METHODS
  The expression of Brachyury was evaluated by PCR and by immunohistochemistry in human lung tumors and adult normal tissues. Brachyury gene copy number and promoter methylation status were analyzed in tumor tissues with various levels of Brachyury expression. Lung carcinoma cells' susceptibility to T-cell lysis and EGF receptor (EGFR) kinase inhibition were also evaluated relative to the levels of Brachyury.
  
  
  RESULTS
  Our results showed Brachyury protein expression in 41% of primary lung carcinomas, including 48% of adenocarcinomas and 25% of squamous cell carcinomas. With the exception of normal testis and some thyroid tissues, the majority of normal tissues evaluated in this study were negative for the expression of Brachyury protein. Brachyury-specific T cells could lyse Brachyury-positive tumors and the level of Brachyury corresponded to resistance of tumor cells to EGFR kinase inhibition.
  
  
  CONCLUSIONS
  We hypothesize that the elimination of Brachyury-positive tumor cells may be able to prevent and/or diminish tumor dissemination and the establishment of metastases. The ability of Brachyury-specific T-cell lines to lyse Brachyury-positive tumor cells, in vitro, supports the development of Brachyury-based immunotherapeutic approaches for the treatment of lung cancer.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Roselli
authors.forename: Romaine I
authors.initials: RI
authors.lastname: Fernando
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
authors.forename: Antonella
authors.initials: A
authors.lastname: Spila
authors.forename: Jhessica
authors.initials: J
authors.lastname: Alessandroni
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palmirotta
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Costarelli
authors.forename: Mary
authors.initials: M
authors.lastname: Litzinger
authors.forename: Duane
authors.initials: D
authors.lastname: Hamilton
authors.forename: Bruce
authors.initials: B
authors.lastname: Huang
authors.forename: Joanne
authors.initials: J
authors.lastname: Tucker
authors.forename: Kwong-Yok
authors.initials: KY
authors.lastname: Tsang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: Claudia
authors.initials: C
authors.lastname: Palena
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D000098908:Brachyury Protein
chemical_list: D066246:ErbB Receptors; D005326:Fetal Proteins; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C512478:EGFR protein, human