Functional Genomics and Proteomics for the understanding of endocrine resistance in Breast Cancer Functional Genomics and Proteomics for the understanding of endocrine resistance in Breast Cancer. Our group is pursuing studies to identify and characterize genes that regulate critical events involved in the development of resistance to anti-estrogens. We found a signature of 67 genes that respond differently to tamoxifen in breast cancer cells that are sensitive compared to resistant ones. When looking at the tumors of women with breast cancer in two different studies, this gene signature predicted disease-free survival in tamoxifen treated patients. We also used robotic approaches to test >500 human kinases (proteins that regulate the activity of other proteins) for their ability to make breast cancer cells resistant to tamoxifen. One of these, HSPB8, repeatedly conferred drug resistance and, by itself, predicted poor clinical outcome in patients. In part, tamoxifen kills breast cancer cells by triggering autophagy, a process by which cells digest their own proteins. Further studies revealed that producing HSPB8 protected breast cancers cells from tamoxifen by preventing autophagy. Conversely, reducing HSBP8 in cells induced autophagy and caused cell death. Expression levels of HSPB8 are reduced after resistant cells are treated with autophagy-inducing drugs, emphasizing the connection between HSPB8 and autophagy. Here we propose to continue with the characterization of the functional role of HSPB8. Through the use of self assembling protein microarrays we will look for interacting partners of HSPB8 to gain a better understanding of its signaling. We are interested to evaluate the effect of HSPB8 in different cancers and less tumorigenic cells.
|Effective start/end date||12/1/09 → 11/30/10|
- Expedition Inspiration Fund for Breast Cancer Research: $10,000.00
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