γ Synuclein, a novel heat-shock protein-associated chaperone, stimulates ligand-dependent estrogen receptor α signaling and mammary tumorigenesis

• Published in: Cancer research (Chicago, Ill.) Vol. 64; no. 13; pp. 4539 - 4546
• Main Authors: YANGFU JIANG, YILIANG ELLIE LIU, GOLDBERG, Itzhak D, SHI, Y. Eric
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-07-2004
• Subjects: Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Estrogen Receptor alpha; gamma-Synuclein; HSP70 Heat-Shock Proteins - metabolism; HSP70 Heat-Shock Proteins - physiology; HSP90 Heat-Shock Proteins - metabolism; HSP90 Heat-Shock Proteins - physiology; Humans; Ligands; Medical sciences; Molecular Chaperones - metabolism; Molecular Chaperones - physiology; Nerve Tissue Proteins - physiology; Pharmacology. Drug treatments; Receptors, Estrogen - metabolism; Receptors, Estrogen - physiology; Signal Transduction - physiology; Synucleins; Transcriptional Activation; Transfection; Tumors; Estrogen receptor α; Signal transduction; Ligand; Chaperone; Heat shock protein; Mammary gland; Carcinogenesis
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-03-3650

Synucleins are emerging as central players in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. gamma synuclein (SNCG), previously identified as a breast cancer-specific gene (BCSG1), is also highly associated with breast or ovarian cancer progression. However, the molecular targets of SNCG aberrant expression in breast cancer have not been identified. Here, we demonstrated a chaperone activity of SNCG in the heat-shock protein (Hsp)-based multiprotein chaperone complex for stimulation of estrogen receptor (ER)-alpha signaling. As an ER-alpha-associated chaperone, SNCG participated in Hsp-ER-alpha complex, enhanced the high-affinity ligand-binding capacity of ER-alpha, and stimulated ligand-dependent activation of ER-alpha. The SNCG-mediated stimulation of ER-alpha transcriptional activity is consistent with its stimulation of mammary tumorigenesis in response to estrogen. These data indicate that SNCG is a new chaperone protein in the Hsp-based multiprotein chaperone complex for stimulation of ligand-dependent ER-alpha signaling and thus stimulates hormone-responsive mammary tumorigenesis.