title: Nerve growth factor overexpression and autocrine loop in breast cancer cells.
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.
authors.affiliation: UPRES-EA-1033, Biologie du Développement, Université des Sciences et Technologies de Lille, IFR-118, Batiment SN3, 59655 Villeneuve d'Ascq, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Dollé
authors.forename: Ikram
authors.initials: I
authors.lastname: El Yazidi-Belkoura
authors.forename: Eric
authors.initials: E
authors.lastname: Adriaenssens
authors.forename: Victor
authors.initials: V
authors.lastname: Nurcombe
authors.forename: Hubert
authors.initials: H
authors.lastname: Hondermarck
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D005260:Female; D006801:Humans; D020932:Nerve Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: D020932:Nerve Growth Factor