Metastasis and Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
Int J Oncol. 2012 Oct;41(4):1541-6. doi: 10.3892/ijo.2012.1581. Epub 2012 Aug 6.
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.
脑源性神经营养因子（BDNF）是神经营养因子超家族的一员，已在神经系统的病理生理学中得到证实，并且在许多神经和心理疾病中具有重要作用。最近，BDNF 也被证明在实体肿瘤骨髓瘤的发展和进展中发挥作用。据报道，BDNF 在人类乳腺癌中异常表达，并且 BDNF 水平升高与不良临床结局和降低的存活率相关。本研究调查了 BDNF 在人类乳腺癌中的作用。使用了一组人乳腺癌细胞，并使用 RT-PCR 评估了 BDNF 的表达谱。我们构建了一组抗 BDNF 转基因，用于转染乳腺癌细胞以产生 BDNF 敲低细胞。评估了 BDNF 敲低对生长和凋亡的影响。使用 SPSS 进行统计分析。P<0.05 被认为具有统计学意义。在乳腺癌细胞系 MCF-7、MDA-MB-231 和 ZR75-1 中成功检测到 BDNF 基因转录本，然后对 MDA-MB-231 和 MCF-7 野生型细胞进行抗 BDNF 转基因的转染，随后建立 BDNF 敲低亚系。在 MDA-MB-231 和 MCF-7 细胞系中敲低 BDNF 导致生长和增殖率降低。对细胞凋亡的分析表明，与载体对照相比，稳定转染 BDNF 核酶的细胞中细胞凋亡增加。结论是，BDNF 是一种神经营养生长因子，在乳腺癌等癌症中异常表达，对乳腺癌细胞的细胞行为有深远影响，并且 BDNF 与乳腺癌细胞凋亡减少有关。BDNF 因此是乳腺癌的潜在治疗靶点，其在人类乳腺癌中的作用需要进一步研究。
