title: Osteopontin Regulates VEGFA and ICAM-1 mRNA Expression in Breast Carcinoma.
abstract: OBJECTIVE
  To analyze the regulatory role of osteopontin on biomarkers associated with cell survival, invasiveness, and angiogenesis mechanisms in a clinical series and breast cancer cell lines.
  
  
  METHODS
  We analyzed by quantitative real-time polymerase chain reaction the messenger RNA (mRNA) expression of osteopontin, Bcl2, intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor A (VEGFA) in several breast cancer cell lines and in 148 breast carcinomas classified into intrinsic subtypes.
  
  
  RESULTS
  We found coexpression of osteopontin, Bcl2, ICAM-1, and VEGFA in triple-negative MDA-MB-468 and MDA-MB-231 cell lines. Furthermore, osteopontin silencing by small interfering RNA inhibited ICAM-1 and VEGFA expression and cell proliferation in MDA-MB-468 cells. In breast cancer specimens, we found a positive correlation between osteopontin, ICAM-1, and VEGFA mRNA expression, especially in triple-negative/basal-like tumors. Among patients with osteopontin-overexpressing tumors, VEGFA remained an independent prognostic indicator for recurrence (hazard ratio, 2.95; 95% confidence interval [CI], 1.48-5.87; P = .002) and death (hazard ratio, 3.25; 95% CI, 1.48-7.11; P = .003) (multivariate analysis, Cox regression).
  
  
  CONCLUSIONS
  Our results support that osteopontin regulates ICAM-1 and VEGFA expression mainly in triple-negative/basal-like breast carcinomas, suggesting a relevant role in the pathogenesis and tumor progression of this molecular subtype. Moreover, VEGFA mRNA levels showed an independent prognostic value in patients with breast cancer.
authors.affiliation: From the Research Unit, fer_om@hotmail.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ortiz-Martínez
authors.affiliation: From the Research Unit.
authors.forename: Elena
authors.initials: E
authors.lastname: Sanmartín
authors.affiliation: From the Research Unit.
authors.forename: Eloy
authors.initials: E
authors.lastname: Pomares-Navarro
authors.affiliation: From the Research Unit.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Pérez-Balaguer
authors.affiliation: Pathology Department, Hospital de Cruces, Barakaldo, Spain; and.
authors.forename: Leire
authors.initials: L
authors.lastname: Andrés
authors.affiliation: Epidemiology Department, and.
authors.forename: José
authors.initials: J
authors.lastname: Sánchez-Payá
authors.affiliation: Pathology Department, University General Hospital of Alicante, Alicante, Spain;
authors.forename: Francisco I
authors.initials: FI
authors.lastname: Aranda
authors.affiliation: Pathology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Lerma
authors.affiliation: From the Research Unit, Pathology Department, University General Hospital of Alicante, Alicante, Spain;
authors.forename: Gloria
authors.initials: G
authors.lastname: Peiró
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D053495:Osteopontin / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C573420:ICAM1 protein, human; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; D018799:Intercellular Adhesion Molecule-1
keywords: Bcl2; Breast carcinoma; ICAM-1; Osteopontin; VEGFA; mRNA expression