Osteopontin Regulates VEGFA and ICAM-1 mRNA Expression in Breast Carcinoma
Objectives: 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) expres...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL) |
| Repositorio: | r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| OAI Identifier: | oai:isabial.fundanetsuite.com:p8111 |
| Acceso en línea: | https://isabial.portalinvestigacion.com/publicaciones8111 |
| Access Level: | acceso abierto |
| Palabra clave: | Bcl2 Breast carcinoma ICAM-1 mRNA expression Osteopontin VEGFA |
| Sumario: | Objectives: 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 I (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. |
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