Abstract 2141: The differential apoptotic responses of normal breast cells versus luminal and triple negative breast cancer cells to chemotherapeutic agents

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 tumors. Since triple negative tumors are missing these established drug targets, there has been little advancement in the establishment of targets in this breast cancer subtype. Triple negative breast cancer is described as aggressive due to their invasiveness and metastatic properties. One potential mediator of triple negative breast cancer aggressive behavior may be due to the fact this breast cancer subtype may have as high as an 80% p53 tumor suppressor gene mutation rate. While p53 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. Here, we stressed a normal breast cancer control, luminal subtype, and triple negative subtype cancer cell lines with Actinomycin D, doxorubicin, and staurosporine. We show that all cell lines responded to the various DNA damaging agents via apoptosis as observed by light microscopy and by PARP cleavage using Western blot analysis. Interestingly, the “normal” breast cell line, AG1132, showed a delayed apoptosis response to doxorubicin treatment as compared to the breast cancer cell lines, HCC1806, HCC70, and HCC1500. We are monitoring the p53 tumor suppressor pathway network in all of these cells to determine its 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. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2141. doi:10.1158/1538-7445.AM2011-2141