title: A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer.
abstract: OBJECTIVE
  Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined.
  
  
  METHODS
  Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk) versus late/nulliparity (high risk).
  
  
  RESULTS
  Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity.
  
  
  CONCLUSIONS
  Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.
authors.forename: Christina Marie
authors.initials: CM
authors.lastname: Gutierrez
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lopez-Valdez
authors.forename: Ramadevi
authors.initials: R
authors.lastname: Subramani
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Arumugam
authors.forename: Sushmita
authors.initials: S
authors.lastname: Nandy
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Rajamanickam
authors.forename: Vignesh
authors.initials: V
authors.lastname: Ravichandran
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Lakshmanaswamy
mesh_terms: D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000517:prevention & control; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019295:Computational Biology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D020543:Proteome; D025521:Tumor Suppressor Proteins