The serum protein profile of early parity which induces protection against breast cancer

• Published in: Oncotarget Vol. 7; no. 50; pp. 82538 - 82553
• Main Authors: Bracamontes, Christina Gutierrez, Lopez-Valdez, Rebecca, Subramani, Ramadevi, Arumugam, Arunkumar, Nandy, Sushmita, Rajamanickam, Venkatesh, Ravichandran, Vignesh, Lakshmanaswamy, Rajkumar
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 13.12.2016
• Subjects: Adult; Apoptosis; Biomarkers - blood; Blood Proteins - analysis; Blotting, Western; Breast Neoplasms - blood; Breast Neoplasms - etiology; Breast Neoplasms - pathology; Breast Neoplasms - prevention & control; Cell Cycle; Cell Proliferation; DNA Damage; Female; Humans; Middle Aged; Parity; Phosphorylation; Predictive Value of Tests; Pregnancy; Protective Factors; Protein Array Analysis; Proteomics - methods; Reproducibility of Results; Research Paper; Risk Assessment; Risk Factors; Signal Transduction; protection; breast cancer risk; serum proteins; biomarkers; parity
• DOI: 10.18632/oncotarget.12757
• ISSN: 1949-2553

Early parity reduces the risk of breast cancer in women while nulliparity and late parity increase the risk of breast cancer. In order to translate this protection to women where early pregnancy is not feasible, much work has focused on understanding how parity confers protection against breast cancer, the molecular mechanisms by which this occurs is still not well understood. Healthy parous and nulliparous women were recruited for this study. We assessed serum protein profiles of early parous, late parous, and nulliparous women using the Phospho Explorer antibody array. Significantly altered proteins identified were validated by Western blot analysis. In silico analysis was performed with the data obtained. Our findings indicate increased phosphorylation levels of CDK1, AKT1 and Epo-R increased cell cycle and cell proliferation in late/nulliparous women. Increased levels of LIMK1, paxillin, caveolin-1, and tyrosine hydroxylase in late/nulliparous women demonstrate enhanced cell stress while decreased activity of p-p53 and pRAD51 in late/nulliparous women indicates decreased apoptosis and increased genomic instability. Further, increased levels of pFAK, pCD3zeta, pSTAT5B, MAP3K8 in early parous women favor enhanced innate/adaptive immunity. Overall, we have identified a unique protein signature that is responsible for the decreased risk of breast cancer and these proteins can also serve as biomarkers to predict the risk of breast cancer.