Identification of ICAM-1 Positive Cells in BRCA1 Deficient Tumors as an Olaparib Resistant Sub-Population

2020 
By Nyiva Muyanga, Biological Sciences; Michael Hass, University of Cincinnati; Syn Yeo, University of Cincinnati Advisor: Jun-Lin Guan Abstract: Breast cancer is the most diagnosed and second most deadly cancer among women, with more than 276,000 cases estimated to be diagnosed in 2020. The BRCA1 (abbreviation for BReast CAncer 1) gene plays a role in preventing the development of breast cancer and is known as a tumor suppressor gene as it slows down cell division and repairs DNA mistakes. Mutations in the BRCA1 gene are the most important known inherited risk factor for breast cancer. Intercellular Adhesion Molecule 1 (ICAM-1) is a protein in humans encoded by the ICAM1 gene. Previous data in our lab has shown that there is a distinct sub-population of ICAM-1 expressing cells in BRAC1 deficient breast tumors. ICAM-1 is found on the surface of cells and can therefore be used to identify cells that express it. Flow cytometry is a technique used to identify and sort cells using surface proteins. In these studies, we utilize flow cytometry to separate cells from BRCA1 deficient breast tumors into populations of ICAM-1 positive and negative cells. We hypothesized that these ICAM-1 positive and negative cells would have different malignant phenotypes and treatment responses. We found that the ICAM-1 positive cells expressed higher levels of Cytokeratin 14 and Collagen 17. We also found that ICAM-1 positive cells were more resistant to treatment with Olaparib, a therapy used in the treatment of BRCA1 deficient breast cancer. In conclusion, our results indicate that ICAM-1 expression demarcates a distinct sub-population of tumor cells with different drug resistant properties.
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