ABSTRACT
Prostate tumor overexpressed-1 (PTOV1), a modulator of the Mediator transcriptional regulatory complex, is expressed at high levels in prostate cancer and other neoplasias in association with a more aggressive disease. Here we show that PTOV1 interacts directly with receptor of activated protein C kinase 1 (RACK1), a regulator of protein kinase C and Jun signaling and also a component of the 40S ribosome. Consistent with this interaction, PTOV1 was associated with ribosomes and its overexpression promoted global protein synthesis in prostate cancer cells and COS-7 fibroblasts in a mTORC1-dependent manner. Transfection of ectopic PTOV1 enhanced the expression of c-Jun protein without affecting the levels of c-Jun or RACK1 mRNA. Conversely, knockdown of PTOV1 caused significant declines in global protein synthesis and c-Jun protein levels. High levels of PTOV1 stimulated the motility and invasiveness of prostate cancer cells, which required c-Jun, whereas knockdown of PTOV1 strongly inhibited the tumorigenic and metastatic potentials of PC-3 prostate cancer cells. In human prostate cancer samples, the expression of high levels of PTOV1 in primary and metastatic tumors was significantly associated with increased nuclear localization of active c-Jun. These results unveil new functions of PTOV1 in the regulation of protein translation and in the progression of prostate cancer to an invasive and metastatic disease.
Subject(s)
Neoplasm Proteins/genetics , Protein Biosynthesis/genetics , Proto-Oncogene Proteins c-jun/genetics , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , COS Cells , Carcinogenesis/genetics , Carcinogenesis/metabolism , Carcinogenesis/pathology , Cell Line , Cell Line, Tumor , Cell Movement/genetics , Chlorocebus aethiops , Disease Progression , Dogs , Humans , Madin Darby Canine Kidney Cells , Male , Mechanistic Target of Rapamycin Complex 1 , Multiprotein Complexes/genetics , Multiprotein Complexes/metabolism , Neoplasm Proteins/metabolism , Prostate/metabolism , Prostate/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Proto-Oncogene Proteins c-jun/metabolism , Receptors for Activated C Kinase , Receptors, Cell Surface , Ribosomes/genetics , Ribosomes/metabolism , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolismABSTRACT
Lytic and blastic lesions have been associated to malignant tumours, such as solid cancer (breast cancer, renal cancer, prostate cancer, malignant melanoma or thyroid tumours). Although a mixed pattern with lytic and blastic lesions is due to metastatic tumour, this is not the only possible origin. The following case shows a systematic. This case report shows the number of tests that were made in order to discover the origin of osteolytic and osteoblastic lesions and it is notable that there is not an occult neoplasia on every occasion (AU)
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Subject(s)
Humans , Female , Aged , Bone Neoplasms/secondary , Mastocytosis, Systemic/diagnosis , Mastocytosis, Systemic/drug therapy , Mastocytosis, Systemic/physiopathology , Osteolysis/drug therapy , Osteolysis/etiology , Osteoporosis/complications , Osteoporosis/drug therapy , Bone Density Conservation Agents/therapeutic use , Anemia/complications , Back Pain/etiology , Diagnosis, Differential , Diphosphonates/therapeutic use , Hypertension/complications , Imidazoles/therapeutic use , Immunologic Factors/therapeutic use , Interferon-alpha/therapeutic use , Magnetic Resonance Imaging/methods , Radionuclide ImagingABSTRACT
La apendicitis aguda es una patología frecuente. Sus complicaciones se relacionan con una estadía hospitalaria prolongada y mayor gasto de recursos, por lo que nos parece relevante buscar índices predictivos de estas complicaciones para poder así establecer medidas preventivas que permitan economizar recursos y acortar la estadía postoperatoria de estos pacientes. Objetivo: Determinar si existió alguna relación entre valores anormales de PCR al ingreso y el desarrollo de complicaciones locales postoperatorias. Material y Método: Estudio descriptivo retrospectivo de una muestra aleatoria de 197 pacientes, operados de apendicitis aguda confirmadas histológicamente, entre el 01-01-1998 y el 31-12-2000 en el Hospital Las Higueras de Talcahuano, relacionando el valor de la PCR al ingreso (normal < 1 mg/I) con la aparición de complicaciones infecciosas locales postoperatoria (infección herida operatoria y/o absceso residual). Resultados: Se encontró un 14,3 por ciento de pacientes con PCR normales de los cuales ninguno presentó complicaciones postoperatorias. Un 85,7 por ciento de los pacientes presentó PCR elevada de los que un 16,6 por ciento presentó complicaciones infecciosas locales en el postoperatorio. Conclusión: Se observó una relación estadísticamente significativa (p < 0,005) entre valores elevados de PCR al ingreso, con la incidencia de complicaciones infecciosas locales postoperatorias.