title: Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression.
abstract: BACKGROUND
  Protein secretion by mammary cells results in autocrine and paracrine signaling that defines cell growth, migration and the extracellular environment. Even so, we have a limited understanding of the cellular processes that regulate protein secretion.
  
  
  METHODS
  In this study, we utilize human epithelial mammary cell (HMEC) lines that were engineered to express different levels of HER1, HER2 and HER3. Using an ELISA microarray platform, we evaluate the effects of epidermal growth factor family receptor (HER) expression on protein secretion in the HMEC lines upon initiation of HER1 receptor activation. The secreted proteins include three HER1 ligands, interleukins 1α and 18, RANTES, vascular-endothelial and platelet-derived growth factors, matrix metalloproteases 1, 2 and 9, and the extracellular portion of the HER1 and HER2 proteins. In addition, we investigate whether MAPK/Erk and PI3K/Akt signaling regulate protein secretion in these cell lines and if so, whether the involvement of HER2 or HER3 receptor alters their response to MAPK/Erk and PI3K/Akt signal pathway inhibition in terms of protein secretion.
  
  
  RESULTS
  Differential expression of HER2 and HER3 receptors alters the secretion of a variety of growth factors, cytokines, and proteases. Some alterations in protein secretion are still observed when MAPK/Erk or PI3K/Akt signaling is inhibited.
  
  
  CONCLUSIONS
  This study suggests that HER overexpression orchestrates broad changes in the tumor microenvironment by altering the secretion of a diverse variety of biologically active proteins.
authors.affiliation: Cell Biology and Biochemistry, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Gonzalez
authors.forename: Richard C
authors.initials: RC
authors.lastname: Zangar
mesh_terms: D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055571:Secretory Pathway / Q000187:drug effects; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; C512478:EGFR protein, human; C508053:ERBB2 protein, human