title: Autoantibodies specific to estrogen receptor alpha act as estrogen agonists and their levels correlate with breast cancer cell proliferation.
abstract: Estrogen receptors have recently been demonstrated at the cell surface. Unlike nuclear receptors, they are able to trigger rapid responses inside the cells. In this study, we evaluated the presence and the possible role of autoantibodies specific to estrogen receptor (anti-ER Abs) in the peripheral blood of breast cancer patients. Anti-ERα Abs were detectable in 22/48 (46%) patients' sera and their levels positively correlated with the percentage of Ki-67-positive breast cancer cells. Anti-ERα Abs purified from breast cancer patients' sera were able: (i) to recognize ERα epitopes expressed at the cell surface of ER-positive breast cancer cells, (ii) to trigger rapid extracellular signal-regulated kinase (ERK) phosphorylation, and (iii) to induce cell proliferation. Our results suggest that anti-ERα Abs can act as estrogen agonists playing a pathogenetic role as breast cancer-promoting factors. These autoantibodies could also be considered as possible peripheral blood biomarkers indicative of the breast cancer growth potential.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Maselli
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Capoccia
authors.affiliation: Department of Medical Oncology, Regina Elena National Cancer Institute , Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pugliese
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Raggi
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cirulli
authors.affiliation: Department of Medical Oncology, Regina Elena National Cancer Institute , Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.affiliation: Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, Rome, Italy; San Raffaele Pisana Institute, Rome, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità , Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Pierdominici
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy; San Raffaele Pisana Institute, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ortona
keywords: Autoantibodies; biomarkers; breast cancer; estrogen receptor; proliferation