RESUMEN
SOCS1-1 is crucial for control of immune cell cytokine expression, including those cytokines known to enable memory T-cell formation and homeostasis. In this study, we found that immunization with SOCS1-downregulated bone marrow-derived dendritic cells generated increased antigen-specific CD8(+) T memory cells and antigen-specific responses, as measured by ELISPOT, CTL assays, serum ELISAs, and T-cell proliferation assays. Bone marrow-derived dendritic cells in which SOCS1 was downregulated expressed increased levels of surface IL-15Ra and thymic leukemia (TL) antigen, both of which support memory cell development. This work supports a crucial role for SOCS1 in regulation of dendritic cell-directed generation of memory T-cell responses.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Regulación hacia Abajo , Memoria Inmunológica , Proteínas Supresoras de la Señalización de Citocinas/biosíntesis , Proteínas Supresoras de la Señalización de Citocinas/inmunología , Animales , Anticuerpos/sangre , Proliferación Celular , Femenino , Citometría de Flujo , Subunidad alfa del Receptor de Interleucina-15/biosíntesis , Subgrupos Linfocitarios/inmunología , Glicoproteínas de Membrana/biosíntesis , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ovalbúmina/inmunología , Proteína 1 Supresora de la Señalización de CitocinasRESUMEN
Breast cancer cells express the chemokine receptor CXCR4 and frequently metastasize to organs with an abundant source of the CXCR4 ligand, stromal cell-derived factor 1 (SDF-1). The chemokine receptor CXCR4 plays an active role in the metastasis of breast cancer. Here, we show that a small interfering RNA (siRNA) against CXCR4 effectively downregulates CXCR4 expression in human MDA-MB-231 breast cancer cells, leading to significant decrease in breast cancer cell invasion and adhesion. It was further found that tumor cells lacking CXCR4 expression proliferated at a much slower rate than control cells in vitro. Surprisingly, tumor cells lacking CXCR4 expression failed to grow in SCID mice in repeated experiments, providing the first direct evidence for an essential role of CXCR4 in breast cancer growth in vivo. This finding suggests an expanded role for the CXCR4 molecule in tumor cell growth in vivo, in addition to its role in breast cancer metastasis. This study implies the CXCR4 molecule as a potential target to control breast tumor growth as well as metastasis.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/fisiopatología , ARN Interferente Pequeño/genética , Receptores CXCR4/biosíntesis , Receptores CXCR4/genética , Animales , Adhesión Celular , Movimiento Celular , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Ratones , Ratones SCID , Invasividad Neoplásica , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
The physicians of today and tomorrow face the most daunting set of regulations ever imposed on the practice of medicine. Through the passage of the Health Insurance Portability and Accountability Act of 1996 (HIPAA), the federal government has thrust its regulatory authority into three of the most controversial and cutting-edge issues in medical practice management: privacy, electronic transactions, and security. Through practical insights, the authors' goal is to introduce physicians to HIPAA's basic tenets, the evolutionary nature of the regulations, and the concept that they can manage HIPAA without bankrupting their practices or sealing themselves away from their patients.
