FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders

BACKGROUND: Fos-related antigen 1 (FRA-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases. METHODS: We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis. RESULTS: FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB) samples. CONCLUSION: The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative breast disorders

Lake Kivu Research: Conclusions and Perspectives

peer reviewedIn this chapter the knowledge gained from the interdisciplinary research on Lake Kivu presented in the previous chapters is synthesized. The importance of the sublacustrine springs as a driving force for physical and biogeochemical processes is highlighted, the special properties of the lake’s food web structure are discussed, and the consequences and impacts of both the introduction of a new fish species and methane extraction are evaluated. Finally, a list of open research questions illustrates that Lake Kivu has by far not yet revealed all of its secrets

Microbial Ecology of Lake Kivu

peer reviewedWe review available data on archaea, bacteria and small eukaryotes in an attempt to provide a general picture of microbial diversity, abundances and microbe-driven processes in Lake Kivu surface and intermediate waters (ca. 0–100 m). The various water layers present contrasting physical and chemical properties and harbour very different microbial communities supported by the vertical redox structure. For instance, we found a clear vertical segregation of archaeal and bacterial assemblages between the oxic and the anoxic zone of the surface waters. The presence of specific bacterial (e.g. Green Sulfur Bacteria) and archaeal (e.g. ammonia-oxidising archaea) communities and the prevailing physico-chemical conditions point towards the redoxcline as the most active and metabolically diverse water layer. The archaeal assemblage in the surface and intermediate water column layers was mainly composed by the phylum Crenarchaeota , by the recently defined phylum Thaumarchaeota and by the phylum Euryarchaeota . In turn, the bacterial assemblage comprised mainly ubiquitous members of planktonic assemblages of freshwater environments (Actinobacteria, Bacteroidetes and Betaproteobacteria among others) and other less commonly retrieved phyla (e.g. Chlorobi, Clostridium and Deltaproteobacteria). The community of small eukaryotes (<5 µm) mainly comprised Stramenopiles , Alveolata , Cryptophyta , Chytridiomycota , Kinetoplastea and Choanoflagellida, by decreasing order of richness. The total prokaryotic abundance ranged between 0.5 × 10^6 and 2.0 × 10^6 cells mL−1 , with maxima located in the 0–20 m layer, while phycoerythrin-rich Synechococcus-like picocyanobacteria populations were comprised between 0.5 × 10^5 and 2.0 × 10^5 cells mL−1 in the same surface layer. Brown-coloured species of Green Sulfur Bacteria permanently developed at 11m depth in Kabuno Bay and sporadically in the anoxic waters of the lower mixolimnion of the main basin. The mean bacterial production was estimated to 336 mg C m−2 day−1 . First estimates of the re-assimilation by bacterioplankton of dissolved organic matter excreted by phytoplankton showed high values of dissolved primary production (ca. 50% of total production). The bacterial carbon demand can totally be fuelled by phytoplankton production. Overall, recent studies have revealed a high microbial diversity in Lake Kivu, and point towards a central role of microbes in the biogeochemical and ecological functioning of the surface layers, comprising the mixolimnion and the upper chemocline

TRIM11 is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth

TRIM11 (tripartite motif-containing protein 11), an E3 ubiquitin ligase, is known to be involved in the development of the central nervous system. However, very little is known regarding the role of TRIM11 in cancer biology. Here, we examined the expression profile of TRIM11, along with two stem cell markers CD133 and nestin, in multiple glioma patient specimens, glioma primary cultures derived from tumors taken at surgery, and normal neural stem/progenitor cells (NSCs). The oncogenic function of TRIM11 in glioma biology was investigated by knockdown and/or over-expression in vitro and in vivo experiments. Our results showed that TRIM11 expression levels were up-regulated in malignant glioma specimens and in high-grade glioma-derived primary cultures, while remaining low in glioblastoma multiforme (GBM) stable cell lines, low-grade glioma-derived primary cultures, and NSCs. The expression pattern of TRIM11 strongly correlated with that of CD133 and nestin, and differentiation status of malignant glioma cells. Knockdown of TRIM11 inhibited proliferation, migration and invasion of GBM cells, significantly decreased EGFR levels and MAPK activity, and down-regulated HB-EGF mRNA levels. Meanwhile, TRIM11 over-expression promoted a stem-like phenotype in vitro (tumorsphere formation) and enhanced glial tumor growth in immunocompromised mice. These findings suggest that TRIM11 might be an indicator of glioma malignancy, and has an oncogenic function mediated through the EGFR signaling pathway. TRIM11 over-expression potentially leads to a more aggressive glioma phenotype, along with increased malignant tumor growth and poor survival. Taken together, clarification of the biological function of TRIM11 and pathways it affects may provide novel therapeutic strategies for treating malignant glioma patients