Nerve growth factor overexpression and autocrine loop in breast cancer cells
Nerve growth factor overexpression and autocrine loop in breast cancer cells
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DOI：
10.1038/sj.onc.1206805
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发表时间：
2003-08-28
期刊：
影响因子：
8
通讯作者：
Hondermarck, H
中科院分区：
文献类型：
--
作者：
Dollé, L;El Yazidi-Belkoura, I;Hondermarck, H
我们在这里显示，神经生长因子（NGF），典型的神经营养因子，是由乳腺癌细胞合成和释放。逆转录-PCR、Western blotting、ELISA和免疫组化检测结果显示，NGF在乳腺癌细胞中有高水平的表达。相反，在正常乳腺上皮细胞中，无论是转录水平还是蛋白水平都不能检测到NGF的产生。共聚焦分析表明经典的分泌囊泡内的NGF的存在。乳腺癌细胞产生的神经生长因子具有生物活性，其诱导胚胎神经前体细胞分化为神经元的能力证明了这一点。重要的是，乳腺癌细胞的组成性生长受到NGF中和抗体或K-252 a（一种NGF受体TrkA的药理学抑制剂）的强烈抑制，表明存在NGF自分泌环。总之，我们的数据表明，神经生长因子在乳腺癌中的生理相关性及其作为标记物和治疗靶点的潜在利益。
We show here that nerve growth factor (NGF), the canonical neurotrophic factor, is synthesized and released by breast cancer cells. High levels of NGF transcript and protein were detected in breast cancer cells by reverse transcription-PCR, Western blotting, ELISA assay and immunohistochemistry. Conversely, NGF production could not be detected in normal breast epithelial cells at either the transcriptional or protein level. Confocal analysis indicated the presence of NGF within classical secretion vesicles. Breast cancer cell-produced NGF was biologically active, as demonstrated by its ability to induce the neuronal differentiation of embryonic neural precursor cells. Importantly, the constitutive growth of breast cancer cells was strongly inhibited by either NGF-neutralizing antibodies or K-252a, a pharmacological inhibitor of NGF receptor TrkA, indicating the existence of an NGF autocrine loop. Together, our data demonstrate the physiological relevance of NGF in breast cancer and its potential interest as a marker and therapeutic target.