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Nerve growth factor overexpression and autocrine loop in breast cancer cells

Oncogene volume 22, pages 5592–5601 (2003)Cite this article

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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Authors and Affiliations

  1. UPRES-EA-1033, Biologie du Développement, Université des Sciences et Technologies de Lille, IFR-118, Batiment SN3, Villeneuve d'Ascq, 59655, France

    Laurent Dollé, Ikram El Yazidi-Belkoura, Eric Adriaenssens & Hubert Hondermarck

  2. School of Biomedical Sciences, University of Queensland, St Lucia, 4072, Australia

    Victor Nurcombe

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  1. Laurent Dollé
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  2. Ikram El Yazidi-Belkoura
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Correspondence to Hubert Hondermarck.

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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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