title: 17β-estradiol regulates giant vesicle formation via estrogen receptor-alpha in human breast cancer cells.
abstract: A significant proportion of the genes regulated by 17-beta-estradiol (E2) via estrogen receptor alpha (ERα) have roles in vesicle trafficking in breast cancer. Intracellular vesicle trafficking and extracellular vesicles have important roles in tumourigenesis. Here we report the discovery of giant (3-42μm) intracellular and extracellular vesicles (GVs) and the role of E2 on vesicle formation in breast cancer (BC) cell lines using three independent live cell imaging techniques. Large diameter vesicles, GVs were also identified in a patient-derived xenograft BC model, and in invasive breast carcinoma tissue. ERα-positive (MCF-7 and T47D) BC cell lines demonstrated a significant increase in GV formation after stimulation with E2 which was reversed by tamoxifen. ERα-negative (MDA-MB-231 and MDA-MB-468) BC cell lines produced GVs independently of E2 and tamoxifen. These results indicate the existence of both intracellular and extracellular vesicles with considerably larger dimensions than generally recognised with BC cells and suggest that the GVs are regulated by E2 via ERα in ERα-positive BC but by E2-independent mechanisms in ER-ve BC.
authors.affiliation: Department of Histopathology, Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Wright
authors.forename: Sarah Bowen
authors.initials: SB
authors.lastname: Jones
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ardern
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ward
authors.forename: Robert B
authors.initials: RB
authors.lastname: Clarke
authors.forename: Federica
authors.initials: F
authors.lastname: Sotgia
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Goran
authors.initials: G
authors.lastname: Landberg
authors.affiliation: Breakthrough Breast Cancer Research Unit, University of Manchester, Manchester, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lamb
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D014162:Transfection; D022161:Transport Vesicles / Q000473:pathology*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol