The Role Of G-Protein Coupled Receptor-Associated Sorting Protein 1 (Gasp-1) In Breast Cancer Progression

An innovative “2-D High Performance Liquid Electrophoresis” (2-D HPLE) technology was used to identify serum biomarkers associated with the earliest stage of breast cancer in addition to other more advanced stages. 2-D HPLE is a newly developed electrophoretic technology that separates 1009s of serum albumin complexes on a polyvinyl membrane based on their surface charges. Association of cancer proteins (biomarkers) with pre-existing albumin complexes in the blood of cancer patients results in altered mobility on the membrane. Using 2-D HPLE we identified that G-protein coupled receptor-associated sorting protein 1(GASP-1) was present in the sera of patients with early stage disease but absent in sera of normal patients. GASP-1 has been shown to modulate lysosomal sorting and functional down-regulation of a variety of G-protein coupled receptors in neuronal cells. However, no reports have linked GASP-1 to breast cancer pathogenesis. GASP-1 was detected in tumor extracts of 7 cases of stage 2 and stage 3 breast cancer but not in adjacent normal tissue as revealed by Western Blot analysis using an antibody developed against a GASP-1 peptide identified by our 2-D HPLE technology. Using this antibody, we immunohistochemically detected over-expression of GASP-1 in all 59 cases of archived ductal breast carcinoma tumor samples. When GASP-1 was silenced in MB-231 breast carcinoma, the cells grew more than 5 fold slower than corresponding vector controls. These studies identify GASP-1 as a potential new serum and tumor biomarker for breast cancer and suggest that GASP-1 may be a novel target for development of breast cancer therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3183. doi:10.1158/1538-7445.AM2011-3183