title: Parity and short-term estradiol treatment utilizes similar cellular mechanisms to confer protection against breast cancer.
abstract: BACKGROUND
  Protective effect of early pregnancy and short-term estrogen treatment (STET), against breast cancer is well established. The underlying mechanisms are not well understood. In this study, we compared the mammary gland cellular microenvironment influenced/induced by parity and STET alongside age-matched controls.
  
  
  METHODS
  Parous, STET, and control rats were injected with N-methyl-N-nitrosourea at 15 weeks and monitored for the development of mammary cancer. A subset of 4 rats were killed five weeks post carcinogen treatment and mammary gland samples were isolated and subjected to molecular analysis.
  
  
  RESULTS
  Our results demonstrated a reduction in cell survival, extracellular matrix associated proliferation, hormonal and growth factor receptor pathways in the experimental groups compared to control rats. Moreover, concomitant reductions in the EMT markers along with cell migration regulators were also observed in parous and STET groups. Hormonal receptor such as GHR, PR, ERα and growth factor receptors IGFR, EGFR and erbB2 were down regulated in the treatment groups. Further analysis revealed that parity and STET drastically reduced the expression, activation of JAK2 and nuclear localization of STATs.
  
  
  CONCLUSIONS
  Parity and STET by targeting major cell signaling pathways involved in cell survival, cell migration and cell death reduces the mammary tumor promoting environment.
authors.affiliation: Center of Excellence in Cancer Research, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Arumugam
authors.forename: Ramadevi
authors.initials: R
authors.lastname: Subramani
authors.forename: Sushmita
authors.initials: S
authors.lastname: Nandy
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lopez
authors.forename: Thiyagarajan
authors.initials: T
authors.lastname: Boopalan
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Lakshmanaswamy
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D053612:Janus Kinases / Q000378:metabolism; D010298:Parity; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000378:metabolism
chemical_list: D050791:STAT Transcription Factors; D004958:Estradiol; D053612:Janus Kinases