Relationship between learning and memory deficits and Arp2 expression in the hippocampus in rats with traumatic brain injury.

OBJECTIVE: To investigate the learning and memory impairments at acute phase after mild traumatic brain injury (TBI) in Sprague-Dawley rats and its relationship with the expression of Arp2. METHODS: Hundred adult male Sprague-Dawley rats were randomly assigned into a TBI group or a control group. TBI was produced by using an impact acceleration model. Learning and memory function was assessed using Morris Water Maze test after different injury intervals, and synaptic function was investigated after TBI treatment by using field excitatory postsynaptic and long-term potentials. Western blot, immunochemistry, and polymerase chain reaction (PCR) were used to detect the mRNA and protein expression of actin-related protein 2 (Arp2) after injury, whereas Nissl staining and DNA ladder assays were performed to detect neuron apoptosis. RESULTS: Using water maze measurement, the authors found escape latency to be significantly higher in the TBI group compared with the control group, and at 7 days postinjury, the difference almost reached up to 30 seconds. Field excitatory postsynaptic potential measurement further found that the long-term potential decreased by nearly 20% in the TBI group compared with the control group, which meant the synaptic excitatory function was downregulated in the TBI group. Further, no significant neuron apoptosis could be detected in the TBI group by Nissl staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and DNA ladder assays. At last, we found that after TBI treatment, the Arp2 mRNA and protein levels were decreased in a time-dependent manner and reached 29.3% and 45.7% of control at 7 days postinjury, separately, and the decrease of mRNA of Arp2 was correlated with delayed escape latency. CONCLUSIONS: This study demonstrated that impairments of learning and memory function in the acute phase after mild TBI may be induced by a reduction in Arp2 expression.

Arp2/3 overexpression contributed to pathogenesis, growth and invasion of gastric carcinoma.

BACKGROUND: Tumor metastasis depends on cell adhesion, motility and deformability, resulting from quantitative alterations and rearrangement of actin-related protein (Arp) 2 and 3. The aim of this study was to clarify the roles of both molecules in tumorigenesis and progression of gastric carcinomas. PATIENTS AND METHODS: Immunohistochemistry (IHC) was employed on tissue microarray containing gastric carcinomas, adjacent metaplasia and gastritis using antibodies against Arp2 and Arp3 with a comparison of their expression with clinicopathological parameters of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for Arp2 and Arp3 protein by IHC. RESULTS: Both proteins were expressed at low levels in gastritis compared with carcinomas (p < 0.05). Arp2 was more frequently expressed in intestinal metaplasia than in carcinoma and gastritis (p < 0.05). Most gastric carcinoma cell lines showed expression at different levels. Expression was positively correlated with tumor size, depth of invasion, venous invasion, Union Internationale Contre le Cancer (UICC) staging and expression of cortactin or fascin (p < 0.05), but not with age, sex, lymphatic invasion or lymph node metastasis (p > 0.05). There was stronger positivity of Arp3 in intestinal- than diffuse-type carcinomas (p < 0.05). A positive relationship between Arp2 and Arp3 proteins was noted (p < 0.05). Univariate analysis indicated that the cumulative survival rate of patients with positive Arp2 or Arp3 expression was not different from those without their expression (p > 0.05). Multivariate analysis showed that age, depth of invasion, lymphatic invasion, lymph node metastasis, UICC staging and Lauren's classification were independent prognostic factors for carcinomas (p < 0.05). CONCLUSION: Aberrant expression of Arp2 and Arp3 is possibly involved in pathogenesis, growth, invasion and progression of gastric carcinomas. Distinct Arp3 expression underlies the molecular mechanisms for the differentiation of intestinal- and diffuse-type carcinomas. They were considered as objective and effective markers to indicate the pathobiological behaviors of gastric carcinomas.

Coexpression of Arp2 and WAVE2 predicts poor outcome in invasive breast carcinoma.

Breast carcinoma with a high histologic grade is highly invasive and metastatic. One reason for its irregular morphology is the formation of excessive protrusions due to assemblages of branched actin filament networks. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein2 (WAVE2), a member of the WASP protein family. In this study, the localization Arp2 and WAVE2 in breast carcinoma was investigated to clarify whether coexpression of the two proteins is associated with histologic grade or patient outcome. Immunohistochemical staining of Arp2 and WAVE2 was performed on mirror specimens of 197 breast carcinomas, and the association between coexpression of the two proteins and clinicopathologic factors was examined. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of Arp2 and WAVE2 coexpression in breast carcinoma. Coexpression of Arp2 and WAVE2 was detected in 64 (36%) of 179 invasive ductal carcinomas and in 2 (11%) of 18 ductal carcinomas in situ, but was not detected in any adjacent non-cancerous tissue. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with high histologic grade (P<0.0001), and cases with lymph node metastasis (P=0.0150). The patients whose cancer cells showed such coexpression had shorter disease-free (P=0.0002) and overall survival (P=0.0122) than patients whose cancer cells expressed only one or none of Arp2 and WAVE2. Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent factor for both tumor recurrence (P=0.0308) and death (P=0.0455). These results indicate that coexpression of Arp2 and WAVE2 is a significant prognostic factor that is closely associated with aggressive morphology of invasive ductal carcinoma of the breast.

Coexpression of actin-related protein 2 and Wiskott-Aldrich syndrome family verproline-homologous protein 2 in adenocarcinoma of the lung.

PURPOSE: Highly invasive and metastatic cancer cells, such as adenocarcinoma of the lung cells, form irregular protrusions by assembling a branched network of actin filaments. In mammalian cells, the actin-related protein 2 and 3 (Arp2/3) complex initiates actin assembly to form lamellipodial protrusions by binding to Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2). In this study, colocalization of Arp2 and WAVE2 in adenocarcinoma of the lung was investigated to elucidate its prognostic value. EXPERIMENTAL DESIGN: Immunohistochemical staining of Arp2 and WAVE2 was done on mirror sections of 115 adenocarcinomas of the lung from pathologic stage IA to IIIA classes. Kaplan-Meier disease-free survival and overall survival curves were analyzed to determine the prognostic significance of the coexpression of Arp2 and WAVE2. RESULTS: Immunoreactivity for both Arp2 and WAVE2 was detected in the same cancer cells in 78 (67.8%) of the 115 lung cancer specimens. The proportion of cancer cells expressing both Arp2 and WAVE2 was significantly higher in cases with lymph-node metastasis (P = 0.0046), and significantly lower in bronchioloalveolar carcinomas (P < 0.0001). The patients whose cancer cells coexpressed them had a shorter disease-free survival time (P < 0.0001) and overall survival time (P < 0.0001). Multivariate Cox regression analysis revealed that coexpression of Arp2 and WAVE2 is an independent risk factor for tumor recurrence. CONCLUSIONS: Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome, and may be involved in the mechanism of cancer metastasis.