Abstract
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.
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Abbreviations
- NGF:
-
nerve growth factor
- NBEC:
-
normal breast epithelial cell
- RT–PCR:
-
reverse transcription–polymerase chain reaction
- SDS–PAGE:
-
sodium dodecyl sulfate–polyacrylamide gel electrophoresis
- ELISA:
-
enzyme-linked immunosorbent assay
- PBS:
-
phosphate-buffered saline
- TBS:
-
tris-buffered saline
- FCS:
-
fetal calf serum
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Acknowledgements
This work was supported by the French Ministry of Research and Education, the ‘Ligue Nationale Contre le Cancer, comité départemental Nord Pas-de-Calais’, the ‘Génopole de Lille’ and the ‘Région Nord-pas-de-Calais’. LD was a recipient of a fellowship from the ‘Ligue Nationale Contre le Cancer’.
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Dollé, L., El Yazidi-Belkoura, I., Adriaenssens, E. et al. Nerve growth factor overexpression and autocrine loop in breast cancer cells. Oncogene 22, 5592–5601 (2003). https://doi.org/10.1038/sj.onc.1206805
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DOI: https://doi.org/10.1038/sj.onc.1206805