The Role of Progesterone Receptor and Glucocorticoid Receptor in the Promotion of Tumorigenesis in BRCA1 Mutation Carriers

Project: Research project

Project Details

Description

The drug RU-486 blocks tumor formation in a mouse model of BRCA1 breast cancer when both copies of the BRCA1 gene are not functional. RU-486 binds strongly to both the progesterone receptor (PR) and glucocorticoid receptor (GCR) and, therefore, blockade of one or both of these receptors may be responsible for the drug’s anti-tumorigenic effect. Gene expression data from BRCA1 mutation carriers, who have one non-functional and one functional copy of BRCA1, reveals that the progesterone receptor pathway does not appear to be activated but GCR expression is significantly up-regulated when compared to normal women (non-carriers). These data have led to the following hypothesis:
Disabling the function of one BRCA1 copy leads to increased signaling through the GCR pathway and disabling of both copies leads to signaling though the PR and/or GCR pathways. This suggests that blockade of GCR in mutation carriers may be more efficacious than PR blockade and that blockade of PR, GCR or both may enable prevention of breast cancer in women in whom both copies are lost. We will test our hypothesis in BRCA1 carriers by interrogating their tissue for the expression of these receptors and will specifically block the receptors in a cell culture model.
StatusFinished
Effective start/end date9/1/158/31/16

Funding

  • Northwestern Memorial Hospital (NMH9102015 Exhibit B.12)

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