PELP1 as a Biomarker for Early Mammary Carcinogenesis

Abstract: 

PELP1 as a Biomarker for Early Mammary Carcinogenesis

This group's long-range goal is to develop tissue biomarkers that can be targeted for the development of novel breast cancer prevention agents, and indicate which high-risk women are likely to benefit from Tam. They are currently studying PELP1 (proline, glutamic acid, and leucine rich protein 1), a nuclear receptor (NR) co-activator, as a biomarker of breast cancer initiation and response to Tam. While most co-activators function in the nucleus to enhance the transcriptional activation function of NRs, PELP1 has been shown to regulate nuclear and extra-nuclear (cytoplasmic) actions of ER. PELP1 subcellular localization is primarily nuclear in normal breast tissue, but it has been shown to be localized to the cytoplasm of  over 50% of PELP1 overexpressing breast tumors. Targeting PELP1 to the cytoplasm by mutation of the nuclear localization signal (PELP-cyto) leads to activation of extra-nuclear signaling and Tam resistance in ER(+) breast cancer cell line models, and breast cancer initiation in a transgenic mouse model. Based on these observations, the researchers hypothesize that cytoplasmic localization PELP1 drives early mammary carcinogenesis and resistance to Tam prevention. They are primarily studying in vitro models of early mammary carcinogenesis and have completed global gene expression analysis of PELP1-cyto expressing cells compared to wild-type PELP1 and vector control. They use MSI resources to analyze or gene expression studies.

 

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