Dollé Laurent, El Yazidi-Belkoura Ikram, Adriaenssens Eric, Nurcombe Victor, Hondermarck Hubert
UPRES-EA-1033, Biologie du Développement, Université des Sciences et Technologies de Lille, IFR-118, Batiment SN3, 59655 Villeneuve d'Ascq, France.
Oncogene. 2003 Aug 28;22(36):5592-601. doi: 10.1038/sj.onc.1206805.
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.
我们在此表明，典型的神经营养因子神经生长因子（NGF）由乳腺癌细胞合成并释放。通过逆转录聚合酶链反应（RT-PCR）、蛋白质印迹法、酶联免疫吸附测定（ELISA）和免疫组织化学在乳腺癌细胞中检测到高水平的NGF转录本和蛋白质。相反，在正常乳腺上皮细胞的转录或蛋白质水平均未检测到NGF的产生。共聚焦分析表明经典分泌囊泡内存在NGF。乳腺癌细胞产生的NGF具有生物活性，这通过其诱导胚胎神经前体细胞神经元分化的能力得以证明。重要的是，NGF中和抗体或NGF受体TrkA的药理学抑制剂K-252a强烈抑制乳腺癌细胞的组成性生长，表明存在NGF自分泌环。总之，我们的数据证明了NGF在乳腺癌中的生理相关性及其作为标志物和治疗靶点的潜在价值。
