A Breast Tissue Protein Expression Profile Contributing to Early Parity-Induced Protection Against Breast Cancer

Abstract

This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. AbstractBackground/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.C. M. Gutierrez and R. Lopez-Valdez contributed equally to this work

Baicalin inhibits breast cancer development via inhibiting IĸB kinase activation in vitro and in vivo

“…NF-κB has been demonstrated to be a key factor enabling precancerous and malignant cells to escape apoptosis (5-7). Inhibition of NF-κB activity results in the partial release of cells from the G2/M arrest after curcumin treatment of MCF-7 cells (8,9). Baicalin is a chemical commonly used to treat diseases of the CNS, hepatic disorders and inflammatory conditions (10,11), and it inhibits lipopolysaccharide-induced inflammation caused by endotoxic shock (12,16).…”

“…This makes NF-κB a key factor in enabling precancerous and malignant cells to escape apoptosis (5)(6)(7). Inhibition of NF-κB activity results in the partial release of cells from the G2/M arrest following curcumin treatment of human breast cancer MCF-7 cells (8,9). Therefore, NF-κB may represent an effective target for controlling tumor invasion and metastasis.…”

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

“…A total of 132 healthy volunteers—44 nulliparous subjects, 44 late parous subjects, and 44 early parous subjects—were recruited for this study [12]. Protein expression profiling was carried out using the Phospho-Explorer protein array.…”

“…Healthy parous and nulliparous women between the ages of 40 and 60 yr. were recruited for this study at the Dr. Susan Love Research foundation in Santa Monica, CA [12]. Protocols for obtaining patient consent to donate venous blood and for the preservation of patient confidentiality, no patient identities were obtained.…”

“…Most recent studies in human subjects and rodent animal models have focused on parity-induced changes at the tissue and cellular level [19–24]. Current studies in human subjects have compared 1) gene expression profiles of mammary tissue from parous and nulliparous women [12, 22]; and 2) gene expression profiles of mammary tissue from premenopausal women undergoing reduction mammoplasty and breast biopsy of benign breast lesions [21]. To our knowledge, the results presented here represent the largest study of completely normal healthy women that includes subjects stratified according to nulliparous, late parous and early parous status.…”