RESUMEN
Homeobox genes encode transcription factors that are essential for normal development and are often dysregulated in cancers. The molecular mechanisms that cause their misregulation in cancers are largely unknown. In this study, we investigate the mechanism by which the Six1 homeobox protein, which has a crucial role during development, is frequently deregulated in several poor outcome, aggressive, metastatic adult human cancers, including breast cancer, ovarian cancer, hepatocellular carcinoma and pediatric malignancies such as rhabdomyosarcoma and Wilms' tumor. Our results reveal that miRNA-185 translationally represses Six1 by binding to its 3'-untranslated region. Analyses of ovarian cancers, pediatric renal tumors and multiple breast cancer cell lines showed decreased miR-185 expression, paralleling an increase in Six1 levels. Further investigation revealed that miR-185 impedes anchorage-independent growth and cell migration, in addition to suppressing tumor growth in vivo, implicating it to be a potent tumor suppressor. Our results indicate that miR-185 mediates its tumor suppressor function by regulating cell-cycle proteins and Six1 transcriptional targets c-myc and cyclin A1. Furthermore, we show that miR-185 sensitizes Six1-overexpressing resistant cancer cells to apoptosis in general and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in particular. Together, our findings suggest that the altered expression of the novel tumor suppressor miR-185 may be one of the central events that leads to dysregulation of oncogenic protein Six1 in human cancers.
Asunto(s)
Progresión de la Enfermedad , Proteínas de Homeodominio/genética , MicroARNs/genética , Neoplasias/genética , Neoplasias/patología , Oncogenes/genética , Regiones no Traducidas 3'/genética , Adulto , Animales , Apoptosis/genética , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica/genética , Proteínas de Homeodominio/metabolismo , Humanos , Masculino , Ratones , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismoRESUMEN
OBJECTIVE: To investigate the rate of pathologically confirmed unfavourable prostate cancers among Korean men who fulfilled the contemporary Epstein criteria for clinically insignificant prostate cancer. PATIENTS AND METHODS: This was a retrospective study of 131 Korean men who underwent radical prostatectomy (RP) for clinically insignificant prostate cancer as defined by contemporary Epstein criteria. We assessed the percentage of unfavourable prostate cancer (pathological Gleason sum > or = 7 and/or extraprostatic extension [EPE]) among these men and tried to identify useful predictors for such unfavourable tumour profiles using uni- and multivariate analyses. RESULTS: Among 131 men with clinically insignificant prostate cancer, 40 (30.5%) had pathological Gleason > or = 7 tumours after RP. Of these 40 men, four (3.1%) also had EPE on examination of RP specimen. All those who did not have Gleason score upgrading after RP had organ-confined disease from examination of RP specimen. Overall, 40 (30.5%) of the 131 men who fulfilled the contemporary Epstein criteria for clinically insignificant prostate cancer before RP had pathologically unfavourable disease. Among our patients, no significant preoperative predictor of pathologically unfavourable disease was identified using uni- and multivariate analyses. CONCLUSION: Our results showed that a significant proportion of contemporary Korean patients who meet all the conditions of the contemporary Epstein criteria for prediction of clinically insignificant prostate cancer might actually harbour prostate cancer with unfavourable pathological features. Such findings should be considered when treatment options are contemplated based upon the Epstein criteria among Asian patients.
Asunto(s)
Neoplasias de la Próstata/patología , Adulto , Anciano , Detección Precoz del Cáncer/métodos , Detección Precoz del Cáncer/normas , Humanos , Corea (Geográfico)/etnología , Masculino , Persona de Mediana Edad , Prostatectomía/métodos , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVES: To investigate whether the presence of detrusor overactivity (DO) influences storage symptoms after photoselective laser vaporization of the prostate (PVP) for benign prostatic hyperplasia (BPH). METHODS: A total of 149 patients who underwent PVP were included in this retrospective study. All patients underwent a preoperative evaluation including multichannel video urodynamics. The efficacy of the PVP was assessed at 1, 3, 6, and 12 months postoperatively using the International Prostate Symptom Score (IPSS), uroflowmetry, postvoid residual urine volume, and 3-day frequency-volume charts (FVC). The patients were stratified into 2 groups (DO group vs non-DO group). RESULTS: The IPSS and FVC showed that the storage symptoms were reduced significantly after the PVP in both groups (P<.05). Starting from 6 months after the PVP, the DO group (n=39) showed a significantly greater reduction in the subtotal storage symptom score than the non-DO group (n=110). When the improvement of storage symptoms was defined as a reduction of >or=50% in the subtotal storage symptom scores, the percentage of patients with improvement in the storage symptoms at 1, 3, 6, and 12 months after the PVP was 13.9%, 25.9%, 47.8%, and 52.9% in the DO group, and 22.2%, 24.4%, 33.3%, and 33.3% in the non-DO group, respectively. CONCLUSIONS: Our results show that storage and voiding symptoms significantly improved after the PVP. In addition, we found that men with DO might show more improvement of storage symptoms, after the PVP, than men without DO.