title: L1CAM is expressed in triple-negative breast cancers and is inversely correlated with androgen receptor.
abstract: BACKGROUND
  Breast cancer is a heterogeneous disease displaying distinct molecular features and clinical outcome. The molecular profile of triple-negative breast cancers (TNBCs) overlaps with that of basal-like breast cancers that in turn show similarities with high-grade serous ovarian and endometrial carcinoma. L1CAM is an established biomarker for the latter cancers and we showed before that approximately 18% of primary breast cancers are positive for L1CAM and have a bad prognosis. Here we analysed the expression of L1CAM breast cancer subtypes.
  
  
  METHODS
  We analyzed mRNA and protein expression data from different breast cancer cohorts for L1CAM, estrogen receptor, progesterone receptor, Her-2 and Androgen receptor (AR) and correlated the data. We performed Western blot analysis on tumor cell lysates and carried out chromatin-immuno-precipitation (CHIP) after AR overexpression.
  
  
  RESULTS
  We find that L1CAM is expressed preferentially though not exclusively in TNBCs. Using the human cancer genome atlas database and two independent breast cancer cohorts we find that L1CAM is inversely correlated with androgen receptor (AR) expression. We found that L1CAM(high)AR(low) primary breast tumors have the worst clinical outcome. Overexpression of AR in MDA-MB436 breast cancer cells decreased L1CAM expression at the protein and mRNA level and CHIP-analysis revealed binding of AR to the L1CAM promoter region.
  
  
  CONCLUSIONS
  These results suggest that L1CAM in breast cancer is under AR control. The data also strongly advocate the use of L1CAM assessment in breast cancer diagnosis. We suggest that L1CAM expression could be causally related to the bad prognosis of TNBCs.
authors.forename: Kai
authors.initials: K
authors.lastname: Doberstein
authors.forename: Karin
authors.initials: K
authors.lastname: Milde-Langosch
authors.forename: Niko P
authors.initials: NP
authors.lastname: Bretz
authors.forename: Uwe
authors.initials: U
authors.lastname: Schirmer
authors.forename: Ayelet
authors.initials: A
authors.lastname: Harari
authors.forename: Isabell
authors.initials: I
authors.lastname: Witzel
authors.forename: Alon
authors.initials: A
authors.lastname: Ben-Arie
authors.forename: Michael
authors.initials: M
authors.lastname: Hubalek
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Müller-Holzner
authors.forename: Susanne
authors.initials: S
authors.lastname: Reinold
authors.forename: Alain G
authors.initials: AG
authors.lastname: Zeimet
authors.affiliation: Tumor Immunology Programme, D015, German Cancer Research Center, Heidelberg, Germany. p.altevogt@dkfz.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.forename: Mina
authors.initials: M
authors.lastname: Fogel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D039842:Neural Cell Adhesion Molecule L1; D012333:RNA, Messenger; D011944:Receptors, Androgen