PELP1: A Potential Biomarker for Breast Cancer Initiation

Adviser: Julie OstranderPELP1 (proline, glutamic acid, leucine rich protein 1), an estrogen receptor coactivator protein, normally localizes in the nucleus of cells; however, PELP1 was found to localize in the cytoplasm in 40% of invasive breast cancers (Vadlamudi et al., 2005). Additionally, a clinical study found that cytoplasmic localization of PELP1 occurs in 36% percent of asymptomatic high-risk women (Girard et al., 2014). Currently, there are no molecular biomarkers that can be used to determine which groups of women with pre-malignant breast lesions will go on to develop invasive breast cancer. For pre-malignant breast lesions to develop into invasive breast cancer, the abnormal cells must acquire epigenetic and genetic changes which result in enhanced migration and invasion to break through the basement membrane (Cowell et al., 2013; Mokbel and Cutuli, 2006; Vargo-Gogola and Rosen, 2007). Here we show that cytoplasmic localization of PELP1 in SUM225 DCIS cells can induce a stem cell phenotype and increased migration. Primary and secondary tumorsphere assays showed increased tumorspheres in SUM225 cells with PELP1 cytoplasmic localization (PELP1-cyto) rather than wild type localization (PELP1-wt). Migration assays showed that that PELP1-cyto cells were trending towards being more migratory that PELP1-wt cells. PELP1 localization in the cytoplasm may be an event in breast cancer initiation for regulating stem cell and migratory phenotypes. Our findings suggest that PELP1 may be able to be used as a biomarker for breast cancer initiation or even a targeted therapy.This research was supported by the Undergraduate Research Opportunities Program (UROP)