title: Pax-5 is a potent regulator of E-cadherin and breast cancer malignant processes.
abstract: Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the development and progression of lymphoid cancers and carcinoma. In contrast to B-cell cancer lesions, the specific expression signatures and roles of Pax-5 in breast cancer progression are relatively unknown. In the present study, we set out to profile Pax-5 expression in mammary tissues and elucidate the cellular and molecular roles of Pax-5 in breast cancer processes. Using immunohistology on mammary tissue arrays, Pax-5 was detected in a total of 298/306 (97.6%) samples tested. Interestingly, our studies reveal that Pax-5 inhibits aggressive features and confers anti-proliferative effects in breast carcinoma cells in contrast to its oncogenic properties in B cell cancers. More precisely, Pax-5 suppressed breast cancer cell migration, invasion and tumor spheroid formation while concomitantly promoting cell adhesion properties. We also observed that Pax-5 inhibited and reversed breast cancer epithelial to mesenchymal phenotypic transitioning. Mechanistically, we found that the Pax-5 transcription factor binds and induces gene expression of E-cadherin, a pivotal regulator of epithelialisation. Globally, we demonstrate that Pax-5 is predominant expressed factor in mammary epithelial cells. We also present an important role for Pax-5 in the phenotypic transitioning processes and aggressive features associated with breast cancer malignancy and disease progression.
authors.affiliation: Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada.|Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.
authors.forename: Sami
authors.initials: S
authors.lastname: Benzina
authors.affiliation: Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada.|Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.
authors.forename: Annie-Pier
authors.initials: AP
authors.lastname: Beauregard
authors.affiliation: Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada.|Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.
authors.forename: Roxann
authors.initials: R
authors.lastname: Guerrette
authors.affiliation: Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada.|Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Jean
authors.affiliation: Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada.|Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.
authors.forename: Mame Daro
authors.initials: MD
authors.lastname: Faye
authors.affiliation: Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada.|Department of Fisheries and Oceans Canada, Molecular Biology Unit, Moncton, NB, E1C 9B6, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Laflamme
authors.affiliation: Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada.|Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.|Georges-L.-Dumont University Hospital Centre, Pathology Department, Moncton, NB, E1C 2Z3, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Maïcas
authors.affiliation: Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Crapoulet
authors.affiliation: Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada.|Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Ouellette
authors.affiliation: Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada.|Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada.
authors.forename: Gilles A
authors.initials: GA
authors.lastname: Robichaud
mesh_terms: D015703:Antigens, CD; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human
keywords: E-cadherin; EMT-MET; Pax-5; breast cancer; metastasis