RESUMEN
Signal transducer and activator of transcription 3 (STAT3) is altered in several epithelial cancers and represents a potential therapeutic target. Here, STAT3 expression, activity and cellular functions were examined in two main histotypes of esophageal carcinomas. In situ, immunohistochemistry for STAT3 and STAT3-Tyr705 phosphorylation (P-STAT3) in esophageal squamous cell carcinomas (ESCC, n=49) and Barrett's adenocarcinomas (BAC, n=61) revealed similar STAT3 expression in ESCCs and BACs (P=0.109), but preferentially activated P-STAT3 in ESCCs (P=0.013). In vitro, strong STAT3 activation was seen by epidermal growth factor (EGF) stimulation in OE21 (ESCC) cells, whereas OE33 (BAC) cells showed constitutive weak STAT3 activation. STAT3 knockdown significantly reduced cell proliferation of OE21 (P=0.0148) and OE33 (P=0.0243) cells. Importantly, STAT3 knockdown reduced cell migration of OE33 cells by 2.5-fold in two types of migration assays (P=0.073, P=0.015), but not in OE21 cells (P=0.1079, P=0.386). Investigation of transcriptome analysis of STAT3 knockdown revealed a reduced STAT3 level associated with significant downregulation of cell cycle genes in both OE21 (P<0.0001) and OE33 (P=0.01) cells. In contrast, genes promoting cell migration (CTHRC1) were markedly upregulated in OE21 cells, whereas a gene linked to tight-junction stabilization and restricted cell motility (SHROOM2) was downregulated in OE21 but upregulated in OE33 cells. This study shows frequent, but distinct, patterns of STAT3 expression and activation in ESCCs and BACs. STAT3 knockdown reduces cell proliferation in ESCC and BAC cells, inhibits migration of BAC cells and may support cell migration of ESCC cells. Thereby, novel STAT3-regulated genes involved in ESCC and BAC cell proliferation and cell migration were identified. Thus, STAT3 may be further exploited as a potential novel therapeutic target, however, by careful distinction between the two histotypes of esophageal cancers.
Asunto(s)
Adenocarcinoma/metabolismo , Esófago de Barrett/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/biosíntesis , Adenocarcinoma/genética , Adenocarcinoma/patología , Esófago de Barrett/genética , Esófago de Barrett/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Ciclo Celular/genética , Procesos de Crecimiento Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Regulación hacia Abajo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Técnicas de Silenciamiento del Gen , Humanos , Fosforilación , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Regulación hacia ArribaRESUMEN
A polarization-diverse subsystem based on periodically poled lithium niobate waveguides is used as an optical phase conjugator for compensation for linear and nonlinear distortion. We show successful transmission formats of 13 x 40 Gbit/s non-return-to-zero mixed with 6 x 10 Gbit/s non-return-to-zero and 40-Gbit/s duobinary over 8 x 100 km of standard single-mode fiber. A single phase conjugator is used to conjugate all data formats, including the alternative duobinary format, simultaneously.