Abstract 4908: The apoptotic response of the triple negative breast cancer cell line HCC1806 to chemotherapeutics

Abstract

Abstract Triple negative breast cancer is characterized by the loss or low expression of estrogen receptor, progesterone receptor, and HER2 proteins which have been targeted and established as somewhat effective therapy regiments in other breast cancer subtypes including luminal breast cancer. Since triple negative tumors are missing these established drug targets, there has been little advancement in the establishment of drug therapies to specifically target this breast cancer subtype. Triple negative breast cancer is described as aggressive due to its invasiveness and metastatic properties. One potential mediator of triple negative breast cancer 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. While the p53 gene may be mutated at high rates, it may be possible to design drugs to target some of the downstream genes that p53 transactivates, including the cyclin dependent kinase inhibitor p21 and the pro-apoptotic gene PUMA, in order to inhibit the further growth of the triple negative breast cancer cells. We previously reported that classic chemotherapeutics including actinomycin-D, staurosporine, and doxorubicin, were effective in eliciting apoptosis in breast cancer cell lines. We initially stressed breast cancer cell lines with all three chemotherapeutics listed above. We showed that all of the cell lines underwent significant apoptosis by 24hrs. Interestingly, the “normal” breast cancer cell line AG11132 had a delayed apoptosis response to doxorubicin treatment as compared to the breast cancer cell lines HCC1806, HCC70 and HCC1500. Therefore, we treated the breast cancer cell lines with a titration of various doxorubicin concentrations. Here we show that even at lower doxorubicin concentrations, a significant amount of apoptosis was measured at 24hrs in all of the cell lines including the triple negative breast cancer cell line HCC1806. We measured apoptosis by the physical characteristics as observed under light microscopy and by using the cell viability assay. We are currently monitoring the p53 tumor suppressor pathway network in all of these cells to determine the network's integrity and whether there is a direct or indirect involvement of p53 on the apoptosis responses. We are also further analyzing the chemotherapeutic agents to determine their effectiveness in killing breast cancer cells with limited cytotoxic effects to normal breast cells at various time-points. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4908. doi:1538-7445.AM2012-4908