Abstract A58: Role of insulin-like growth factor binding protein acid labile complex in ER-PR- Her2+ breast cancer in African American women.

Abstract

The emergence of the obesity epidemic worldwide has been associated with increases in breast cancer and type 2 diabetes. Symptoms associated with obesity collectively known as metabolic syndrome have been associated with triple negative breast tumors that are common among premenopausal women, especially those of African American (AA) descent. The insulin-leptin adiponectin axis has been implicated in these breast tumors that are insensitive to estrogen. It is suggested that insulin, insulin like growth factors and epidermal growth factors mediate the interactions between these hormones. Previous studies have shown that insulin like growth factor 2 (IGF-2) synergistically cross-talks with estrogen receptor (ER) alpha and ER-beta to promote estrogen independent breast cancer progression. This suggests that IGF-2 can activate insulin like growth factor I (IGF-1) receptor and insulin receptor to activate both ER alpha and ER beta in breast cancer cells leading to proliferation and tumorigenesis. The purpose of this study was to find the the role of insulin-like growth factor binding protein acid labile complex (IGFBP-ALS) identified in our previous serum proteomic pilot study that included six AA breast cancer women and six healthy AA controls. Methods: The serum samples were processed on IgY12 (Beckman) antibody column to remove the top 12 proteins. The flow through fraction was digested using trypsin for LC/MS analysis. The protein digest serum samples were analyzed in triplicate on a high performance LTQFT (Thermo Electron) mass spectrometer coupled to an online Surveyor LC system equipped with an autosampler. Samples were loaded onto a trap column using a sample pump. An MS pump was used for eluting the peptides onto an analytical column for further separation and online nano-ESI LC/MS/MS analysis. The raw MS data files were imported into DeCyderMS (GE Healthcare) module and data were processed for peptide/protein expression analysis. Results: DeCyderMS analysis revealed significant differences in the expression of 215 peptides between the two groups (t-test: < 0.05; ave fold ratio: <0.5 or >2). Most of these peptides were mapped to 28 proteins in the Swiss-Prot database. DecyderMS analyses on all the replicates from each sample are underway to identify the peptide pattern differences between the healthy and cancer samples. Among other differentially expressed proteins IGFBP-ALS was significantly low in sera from African American women with breast cancer with tumors possessing the ER-PR-Her2+receptor status. In a previous study, 60% of the women from the same cohort experienced metabolic syndrome. Conclusions: It is suggested that IGFBP-ALS is necessary for the binding of IGF-1 or IGF-2 to the plasma IGF protein BP-53. Low levels of IGFBP-ALS subunit in the sera of ER-PR-HER2+ AA cancer patients could serve as biomarker for early-stage, breast cancer with aggressive features. Additionally this protein could reveal an association between obesity and breast cancer. Efforts are currently underway to validate this biomarker to gain insight into the etiology of aggressive breast tumors in AA women.

Funded by The Susan G. Komen For the Cure Breast Cancer Foundation.

Citation Format: Padma Uppala. Role of insulin-like growth factor binding protein acid labile complex in ER-PR- Her2+ breast cancer in African American women. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A58.