Biological influence of brain-derived neurotrophic factor on breast cancer cells

Abstract

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin superfamily which has been indicated in the pathophysiology of the nervous system and is important in a number of neurological and psychological conditions. Recently, BDNF was also shown to play a role in the development and progression of solid tumour myeloma. It has been reported that BDNF is 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 investigated the role of BDNF in human breast cancer. A panel of human breast cancer cells was used and 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 knocked down cells. The impact of BDNF knockdown on growth and apoptosis was evaluated. Statistical analysis was performed using SPSS. P<0.05 was considered statistically significant. BDNF gene transcripts were successfully detected in the breast cancer cell lines MCF-7, MDA-MB-231 and ZR75-1 MDA-MB-231 and MCF-7 wild-type cells were subject to transfection of anti-BDNF transgenes, followed by the establishment of BDNF knocked down sublines. Knockdown of BDNF in MDA-MB-231 and MCF-7 cell lines resulted in decreased rates of growth and proliferation. Analysis of apoptosis showed that cell apoptosis was increased in 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 BDNF is associated with a reduction of the apoptosis of breast cancer. BDNF is, therefore, a potential therapeutic target in breast cancer and its effect in human breast cancer requires further investigation.