title: Estrogen receptor expression and gene promoter methylation in non-small cell lung cancer - a short report.
abstract: OBJECTIVE
  In the past, anomalous estrogen receptor (ER) regulation has been associated with various lung pathologies, but so far its involvement in lung cancer initiation and/or progression has remained unclear. Here, we aimed at assessing in vivo and in vitro ER expression and its possible epigenetic regulation in non-small cell lung cancer (NSCLC) samples and their corresponding normal tissues and cells.
  
  
  METHODS
  ERα and ERβ gene expression levels were assessed using real time quantitative PCR (RT-qPCR), whereas ERα and ERβ gene promoter methylation levels were assessed using DNA bisulfite conversion followed by pyrosequencing. We included NSCLC (n = 87) and adjacent histologically normal lung tissue samples from lung cancer patients (n = 184), primary normal bronchial epithelial-derived cell cultures (n = 11), immortalized bronchial epithelial-derived cell lines (n = 3) and NSCLC derived cell lines (n = 9).
  
  
  RESULTS
  Using RT-qPCR we found significantly lower ERα and ERβ expression levels in the NSCLC tissue samples compared to their normal adjacent tissue samples. These lower ER expression levels were confirmed in vitro using primary normal bronchial epithelial-derived cell cultures, immortalized bronchial epithelial-derived cell lines and NSCLC-derived cell lines. By using this latter panel of cells, we found that ER gene promoter hypermethylation was associated with decreased ER expression. In addition we found that in tumor and normal lung tissues, smoking was associated with decreased ER expression and that normal lung tissues with a low ERβ expression level exhibited increased smoking-related DNA adducts.
  
  
  CONCLUSIONS
  Taken together, our results indicate that decreased ER expression mediated by DNA methylation may play a role in NSCLC development.
authors: Section for Toxicology and Biological Working Environment, Department of Biological and Chemical Working Environment, National Institute of Occupational Health, PO box 8149, Dep., Gydas vei 8, N-0033, Oslo, Norway. xavier.tekpli@medisin.uio.no.|Department of Genetics, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital, Oslo, Norway. xavier.tekpli@medisin.uio.no.
authors: Xavier
authors: http://orcid.org/0000-0003-4042-8290
authors: X
authors: Tekpli
authors: Section for Toxicology and Biological Working Environment, Department of Biological and Chemical Working Environment, National Institute of Occupational Health, PO box 8149, Dep., Gydas vei 8, N-0033, Oslo, Norway.
authors: Vidar
authors: V
authors: Skaug
authors: Section for Toxicology and Biological Working Environment, Department of Biological and Chemical Working Environment, National Institute of Occupational Health, PO box 8149, Dep., Gydas vei 8, N-0033, Oslo, Norway.
authors: Rita
authors: R
authors: Bæra
authors: Analytical and Environmental Sciences, MRC-PHE Centre for Environment and Health, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK.
authors: David H
authors: DH
authors: Phillips
authors: Section for Toxicology and Biological Working Environment, Department of Biological and Chemical Working Environment, National Institute of Occupational Health, PO box 8149, Dep., Gydas vei 8, N-0033, Oslo, Norway.
authors: Aage
authors: A
authors: Haugen
authors: Section for Toxicology and Biological Working Environment, Department of Biological and Chemical Working Environment, National Institute of Occupational Health, PO box 8149, Dep., Gydas vei 8, N-0033, Oslo, Norway.
authors: Steen
authors: S
authors: Mollerup
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D011960:Receptors, Estrogen
keywords: DNA adducts; DNA methylation; Estrogen receptor; Gene expression; Lung cancer