CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
artículos
Título:
Immunoglobulin G from Breast Cancer Patients in Stage I Stimulates Muscarinic Acetylcholine Receptors in MCF7 Cells and Induces Proliferation. Participation of Nitric Oxide Synthase-Derived Nitric Oxide.
Autor/es:
NEGRONI MARIA PIA; FISZMAN GABRIEL L; AZAR ME; MORGADO CC; ESPAÑOL ALEJANDRO JAVIER; PELEGRINA LAURA TATIANA; DE LA TORRE EULALIA; SALES MARÍA ELENA
Revista:
JOURNAL OF CLINICAL IMMUNOLOGY
Editorial:
Springer
Referencias:
Lugar: Netherlands; Año: 2010 p. 474 - 484
ISSN:
0271-9142
Resumen:
NTRODUCTION: Muscarinic acetylcholine receptors (mAChR) belong to the
G-protein-coupled receptor family and are extensively expressed in most
cells in mammals. We had reported the expression of mAChR in murine and
human breast tumors. METHODS: The presence of antibodies in the sera of
patients with different tumors directed against self-proteins has been
recently described. In this work, we investigated the presence of
autoantibodies against mAChR in the sera of breast cancer patients in
stage I (T1N0Mx-IgG). IgG purification was performed by affinity
chromatography in protein G-agarose. We also studied the ability of
these antibodies to modulate the proliferation of MCF-7 breast tumor
cells by the MTS colorimetric assay. The ability of T1N0Mx-IgG to
stimulate muscarinic signaling pathway via nitric oxide synthase was
tested by Griess reaction. RESULTS: We demonstrated M(3) and M(4)
receptors expression in MCF-7 cells. T1N0Mx-IgG promotes cell
proliferation, mimicking the action of the muscarinic agonist carbachol.
This effect was preferentially due to M(3) receptor activation in tumor
cells via phospholipase C-induced nitric oxide liberation by
calcium-dependent nitric oxide synthases. IgG from control patients was
unable to produce this effect. DISCUSSION: IgG from patients with breast
cancer in early stages could be promoting tumor progression by
muscarinic activation, and its presence could be determining the
prognosis of this illness.