Abigail Sproull

Identification of PELP1 regulated pathways that enhance mammary stem cell activity

Breast cancer is the second leading cause of cancer death among women, however, its mortality rate has decreased significantly due to better treatments, increased awareness, and earlier screening. Proline, glutamic acid, leucine rich protein 1 (PELP1) is an estrogen receptor coactivator that serves as a potential biomarker for breast cancer initiation as it has been shown that cytoplasmic PELP1 signaling and associated protein complexes promote cancer stem cell expansion and self-renewal in ER+ breast cancers. Mammosphere assays of normal epithelial cells also suggest that PELP1 plays a role in promoting mammary stem cell self-renewal. To better understand PELP1-induced pathways that promote mammary stem cell self-renewal and differentiation, the Ostrander lab performed RNA sequencing (RNA-seq) on RNA isolated from MCF10A cells, a model of normal mammary epithelial cells, cultured in standard 2D and 3D mammosphere conditions. RNA-seq results from MCF10A cells expressing either cytoplasmic, wild-type, or vector control PELP1 were analyzed in Ingenuity Pathway Analysis (IPA) to identify cytoplasmic PELP1 regulated pathways. IPA suggests that Wnt/β-catenin and TGFβ signaling is significantly upregulated in cytoplasmic PELP1 expressing cells cultured in mammosphere conditions. Both of these signaling pathways play important roles in stem cell biology, with Wnt/β-catenin regulating stem cell pluripotency and TGFβ promoting epithelial-mesenchymal transition. Genes upregulated in these pathways include FZD1, WNT11, CTNNB1 for Wnt/β-catenin and BMP4, TGFB1, TGFB3 for TGFβ are being validated on the mRNA and protein level. Future studies will focus on how the inhibition of these pathways impact mammary stem cell biology.

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