For a patient diagnosed with breast cancer, the determination of a treatment is based on a biopsy and the markers that are present in the tumor at the time of diagnosis. There are tumors that are difficult to determine whether or not it will respond to chemotherapy treatment at the time of diagnosis. The research that I have been working on supports the main goal of the Skildum lab that discovering predictive biomarkers in tumor samples will help to determine a personalized and more effective treatment path. To model drug resistant breast cancer in vitro, I work with MCF-7
(sensitive to chemotherapy treatment) and LCC9 (less sensitive to chemotherapy treatment) breast cancer cells. Tfam is the major regulator of mitochondrial DNA replication and transcription. I discovered that the Tfam gene had an increased expression in the LCC9 cells than in the MCF-7 cells. We then decided to look at the contribution of Tfam expression to drug
sensitivity in LCC9 cells. Through siRNA transfection, which interferes with the translation of proteins by binding and promoting degradation of the messenger RNA at specific sequences, we successfully knocked down Tfam mRNA expression. Here we show the consequences of Tfam knockdown are decreased mitochondrial DNA copy number and decreased labeling with a mitochondria specific fluorescent dye. From this finding I have begun to test whether Tfam knockdown in LCC9 cells increases their sensitivity to the chemotherapy drug doxorubicin. If LCC9 cells do have increased drug sensitivity after Tfam knockdown, then the Tfam gene could potentially be used as a biomarker of drug resistance in breast cancer patients.
This research was supported by the Undergraduate Research Opportunities Program (UROP).
Manipulating Tfam expression and mitochondrial capacity to overcome drug resistance in breast cancer cells..
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