PMID- 25116349 OWN - NLM STAT- MEDLINE DCOM- 20150413 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 34 IP - 2 DP - 2014 TI - Parity and short-term estradiol treatment utilizes similar cellular mechanisms to confer protection against breast cancer. PG - 491-505 LID - 10.1159/000363017 [doi] AB - 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, ERalpha 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. CONCLUSION: Parity and STET by targeting major cell signaling pathways involved in cell survival, cell migration and cell death reduces the mammary tumor promoting environment. CI - (c) 2014 S. Karger AG, Basel. FAU - Arumugam, Arunkumar AU - Arumugam A AD - 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. FAU - Subramani, Ramadevi AU - Subramani R FAU - Nandy, Sushmita AU - Nandy S FAU - Lopez, Rebecca AU - Lopez R FAU - Boopalan, Thiyagarajan AU - Boopalan T FAU - Lakshmanaswamy, Rajkumar AU - Lakshmanaswamy R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140808 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (STAT Transcription Factors) RN - 4TI98Z838E (Estradiol) RN - EC 2.7.10.2 (Janus Kinases) SB - IM MH - Animals MH - Breast Neoplasms/enzymology/metabolism/*prevention & control MH - Estradiol/administration & dosage/*pharmacology MH - Female MH - Janus Kinases/metabolism MH - *Parity MH - Rats MH - Rats, Sprague-Dawley MH - Real-Time Polymerase Chain Reaction MH - STAT Transcription Factors/metabolism EDAT- 2014/08/15 06:00 MHDA- 2015/04/14 06:00 CRDT- 2014/08/14 06:00 PHST- 2014/06/10 00:00 [accepted] PHST- 2014/08/14 06:00 [entrez] PHST- 2014/08/15 06:00 [pubmed] PHST- 2015/04/14 06:00 [medline] AID - 000363017 [pii] AID - 10.1159/000363017 [doi] PST - ppublish SO - Cell Physiol Biochem. 2014;34(2):491-505. doi: 10.1159/000363017. Epub 2014 Aug 8.