P2-01-21: The Biological Influence of Brain Derived Neurotrophic Factor (BDNF) on the Aggressiveness of Human Breast Cancer Cells.

Abstract

Introduction: Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin superfamily and has been indicated in the pathophysiology of the nervous system and is important in a number of neurological and psychological conditions. Recently, BDNF has also been shown to play a role in the development and progression of solid tumours myeloma, lung cancer and prostate cancer. It has been recently reported that BDNF is also aberrantly expressed in human breast cancer and that a raised level of BDNF is associated with poor clinical outcome and reduced survival. The present study aimed to investigate the biological role of BDNF in human breast cancer. Materials and methods: A panel of human breast cancer cells were used in the present study. The expression profile of BDNF was evaluated using RT-PCR. We constructed a set of anti-BDNF transgenes which were used to transfect breast cancer cells in order to generate BDNF knockdown cells (MCFΔBDNF). The impact of BDNF knockdown on growth and cellular migration were evaluated using standard growth assays and ECIS (electronic cell impedance sensing) technology. Results: BDNF gene transcripts were successfully detected in the breast cancer cell lines, MCF-7, MDA MB-231 and ZR 75-1. MCF-7 wild type cells were subject to transfection of anti-BDNF transgenes, followed by the establishment of BDNF knockdown sub-lines and empty vector control cells (MCFpef). Loss of BDNF in breast cancer cells resulted in reduction of cell growth rate (growth rate in MCFΔBDNF by day 3 1.60+/−0.11, compared with 2.06+/−0.04 in MCFpef, p=0.006). Using electric cell-substrate impedance sensing, it was found that loss of BDNF in breast cancer cells resulted in a significant increase in the rate of cellular attachment and migration (migration rate over 14 h in ohms: MCFΔBDNF 6310.125+/−595.183 compared with MCFpef 5115.5 +/−422.394, p=0.0003). Conclusion: When BDNF was stably knocked down in MCF-7 cell lines, the growth and proliferation were decreased. The ECIS results also showed that cell migration was decreased in MCF-7 cells stably transfected with ribozymes for BDNF compared with the vector control. It is concluded that BDNF, a neurotrophic growth factor aberrantly expressed in cancers such as breast cancer, has a profound impact on the cellular behaviour of breast cancer cells and that loss of BDNF is associated with a reduction of the aggressiveness of breast cancer. BDNF is therefore a potential therapeutic target in breast cancer and its effect in human breast cancer requires further investigation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-21.