Abstract 5879: Establishing doxorubicin resistant HCC1806 triple negative breast cancer cell lines result in the differential expression of let7a and miR34a

Abstract

Abstract Resistance to chemotherapy is one of the major difficulties in the treatment of triple negative breast cancer. Besides the typical known causes of drug resistance, tumor microenvironment can also promote resistance by preventing the drug from accumulating in tumor cells in order to elicit a cytotoxic response. TNBC is characterized by the loss or low expression of estrogen receptor, progesterone receptor, and HER2 proteins that have been targeted and established as somewhat effective therapy regiments in other breast cancer subtypes including liminal breast cancer. Since TNBC tumors are missing these well-known drug targets, there is little to no advancement in the establishment of drug therapies to accurately target this breast cancer subtype. TNBC is termed as aggressive due to the fact of its invasiveness and metastatic properties. One potential mediator of TNBC aggressive behavior may be due to the fact that this breast cancer subtype may have as high as an 80% p53 tumor suppressor gene mutation rate which may also play a role in the ability of TNBC to recur as a result of the inability to kill all remaining TNBC cells leading to chemotherapy resistance. In these studies, we hope to mimic TNBC recurrence by establishing doxorubicin resistant HCC1806 TNBC cell lines. Here we show that we were able to sustain TNBC cell growth after pulse treatments with increasing concentrations of doxorubicin, and we revealed that p53-related miRNAs, let7a and miR34a, were differentially expressed after pulse treating the HCC1806 cells. Understanding the molecular and mechanistic factors related to recurrence and doxorubicin-resistance in HCC1806 cells may help to develop a list of possible targets for molecular therapy to overwhelm tumor drug resistance in triple negative breast cancer and may develop or establish a list of potential targets for disabling, or combating resistance to doxorubicin treatment in TNBC patients. Note: This abstract was not presented at the meeting. Citation Format: Checo J. Rorie, Malcolm M. Moses, Mohammed K. Musa, Sherette S. Godfrey. Establishing doxorubicin resistant HCC1806 triple negative breast cancer cell lines result in the differential expression of let7a and miR34a [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5879. doi:10.1158/1538-7445.AM2017-5879