A breast tissue protein expression profile contributing to early parity-induced protection against breast cancer Journal Article
| Authors: | Gutierrez, C. M.; Lopez-Valdez, R.; Subramani, R.; Arumugam, A.; Nandy, S.; Rajamanickam, V.; Ravichandran, V.; Lakshmanaswamy, R. |
| Article Title: | A breast tissue protein expression profile contributing to early parity-induced protection against breast cancer |
| Abstract: | Background/Aims: 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. © 2015 S. Karger AG, Basel. |
| Keywords: | immunohistochemistry; signal transduction; adult; controlled study; human tissue; protein expression; major clinical study; cancer risk; biomarkers; dna damage; cancer prevention; apoptosis; breast cancer; gene expression profiling; breast; epidermal growth factor receptor; inflammation; mitogenesis; protein; immunoglobulin enhancer binding protein; protein tyrosine kinase; brca1 protein; protein p53; genomic instability; down regulation; epidermal growth factor receptor 3; cell cycle regulation; bioinformatics; data analysis software; intercellular adhesion molecule 1; prevention; rad52 protein; first trimester pregnancy; parity; nullipara; activating transcription factor 1; activating transcription factor; protein fos; aurora kinase; low risk population; human; female; priority journal; article |
| Journal Title: | Cellular Physiology and Biochemistry |
| Volume: | 37 |
| Issue: | 5 |
| ISSN: | 1015-8987 |
| Publisher: | Cell Physiol Biochem Press |
| Date Published: | 2015-11-01 |
| Start Page: | 1671 |
| End Page: | 1685 |
| Language: | English |
| DOI: | 10.1159/000438533 |
| PROVIDER: | scopus |
| PUBMED: | 26536102 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 7 January 2016 -- Source: Scopus |
