title: Loss of aquaporin-4 expression and putative function in non-small cell lung cancer.
abstract: BACKGROUND
  Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs.
  
  
  METHODS
  We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry.
  
  
  RESULTS
  Variable expression of several AQPs (AQP1, -3, -4, and -5) was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue.
  
  
  CONCLUSIONS
  Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets.
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Germany. arne.warth@med.uni-heidelberg.de
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.forename: Thomas
authors.initials: T
authors.lastname: Muley
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Anita
authors.initials: A
authors.lastname: Pathil
authors.forename: Hans
authors.initials: H
authors.lastname: Hoffmann
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Schnabel
authors.forename: Christian
authors.initials: C
authors.lastname: Bender
authors.forename: Andreas
authors.initials: A
authors.lastname: Buness
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Ruprecht
authors.initials: R
authors.lastname: Kuner
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000077192:Adenocarcinoma of Lung; D051401:Aquaporin 4 / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D040081:Protein Array Analysis
chemical_list: D051401:Aquaporin 4