Phosphorylation of RSK2 at Tyr529 by FGFR2-p38 enhances human mammary epithelial cells migration

The members of p90 ribosomal S6 kinase (RSK) family of Ser/Thr kinases are downstream effectors of MAPK/ERK pathway that regulate diverse cellular processes including cell growth, proliferation and survival. In carcinogenesis, RSKs are thought to modulate cell motility, invasion and metastasis. Herein, we have studied an involvement of RSKs in FGF2/FGFR2-driven behaviours of mammary epithelial and breast cancer cells. We found that both silencing and inhibiting of FGFR2 attenuated phosphorylation of RSKs, whereas FGFR2 overexpression and/or its stimulation with FGF2 enhanced RSKs activity. Moreover, treatment with ERK, Src and p38 inhibitors revealed that p38 kinase acts as an upstream RSK2 regulator. We demonstrate for the first time that in FGF2/FGFR2 signalling, p38 but not MEK/ERK, indirectly activated RSK2 at Tyr529, which facilitated phosphorylation of its other residues (Thr359/Ser363, Thr573 and Ser380). In contrast to FGF2-triggered signalling, inhibition of p38 in the EGF pathway affected only RSK2-Tyr529, without any impact on the remaining RSK phosphorylation sites. p38-mediated phosphorylation of RSK2-Tyr529 was crucial for the transactivation of residues located at kinase C-terminal domain and linker-region, specifically, in the FGF2/FGFR2 signalling pathway. Furthermore, we show that FGF2 promoted anchorage-independent cell proliferation, formation of focal adhesions and cell migration, which was effectively abolished by treatment with RSKs inhibitor (FMK). These indicate that RSK2 activity is indispensable for FGF2/FGFR2-mediated cellular effects. Our findings identified a new FGF2/FGFR2-p38-RSK2 pathway, which may play a significant role in the pathogenesis and progression of breast cancer and, hence, may present a novel therapeutic target in the treatment of FGFR2-expressing tumours.     

Common variants of xeroderma pigmentosum genes and prostate cancer risk

The genetic basis of prostate cancer (PC) is complex and appears to involve multiple susceptibility genes. A number of studies have evaluated a possible correlation between several NER gene polymorphisms and PC risk, but most of them evaluated only single SNPs among XP genes and the results remain inconsistent. Out of 94 SNPs located in seven XP genes (XPA–XPG) a total of 15 SNPs were assayed in 720 unselected patients with PC and compared to 1121 healthy adults. An increased risk of disease was associated with the XPD SNP, rs1799793 (Asp312Asn) AG genotype (OR = 2.60; p < 0.001) and with the AA genotype (OR = 531; p < 0.0001) compared to the control population. Haplotype analysis of XPD revealed one protective haplotype and four associated with an increased disease risk, which showed that the A allele (XPD rs1799793) appeared to drive the main effect on promoting prostate cancer risk. Polymorphism in XPD gene appears to be associated with the risk of prostate cancer.     

Age-related limitations of interleukin-6 in predicting early mortality in acute ST-elevation myocardial infarction

Interleukin-6 (IL-6) is an inflammatory cytokine whose levels increase significantly during myocardial infarction (MI).It has been hypothesised that the concentrations of IL-6 at admission may be useful in prognosticating long-term outcomes. It is unclear, however, whether IL-6 could improve the prognosis of early mortality in MI.We have compared serum IL-6 levels and analysed the disease course in 158 patients with ST-elevation MI (STEMI) who either survived (n?=?148) or died (n?=?10) within 30 days following the admission. Patients were treated in a single university centre with primary percutaneous coronary intervention (PCI).The non-survivors (6.3%) displayed most of typical risk factors for poor outcome. In addition they had significantly higher concentrations of IL-6 at hospital admission (median values 8.5 vs. 2.0 pg/ml; p?=?0.038). However, they were also significantly older than the survivors (median values 72 vs. 57 years; p?=?0.0001). IL-6 levels are known to increase with age and we could confirm a significant correlation between patients’ calendar age and circulating IL-6 (p?=?0.009). Regression analysis revealed that IL-6 concentrations were significantly affected by patients’ age but they did not independently relate to patients’ outcome.Such results indicate that circulating IL-6 at admission may be of limited value in predicting early mortality in STEMI. It is important to recognize that, because of the small group of patients who died (N?=?10), the results must be interpreted with caution. Therefore, we stress that these results should be viewed as preliminary and further validated in a larger set of patients.     

The pleiotropic effects of extract containing rhizobial Nod factors on pea growth and yield

Rhizobial lipochitooligosacharides (Nod factors) influence the development of legume roots, including growth stimulation, nodule induction and root hair curling. However, their effect on the green parts of plants is less known, therefore we evaluated seed and foliar application of an extract containing Nod factors on pea growth and yield. Pea plants were examined from emergence to full maturity, including growth dynamics and morphological (nodule number and weight, the quantity and surface area of leaves) or physiological (photosynthesis and transpiration intensity, chlorophyll and nitrogen content) parameters. The foliar application Nod factor extract, or seed dressing followed by foliar application, resulted in the best outcomes. The number and weight of root nodules, the chlorophyll content in leaves, and the intensity of net photosynthesis were all elevated. As a consequence of Nod factor treatment, the dynamics of dry mass accumulation of pea organs were improved and the pod number was increased. A significant increase in pea yield was observed after Nod factor application. Increase of nodule and pod numbers and improved growth of roots appear to be amongst the beneficial effects of Nod factor extract on the activation of secondary plant meristems.     

Anoctamin-1 in the Juvenile Rat Urinary Bladder

Purpose

To investigate presence, location and functional role of calcium-activated chloride channel (CaCC) Anoctamin-1 (Ano1) in rat urinary bladder.

Materials and Methods

Bladders from 3 week old Wistar rats were studied. End-point PCR on total mRNA was used to assess the expression of Ano1. Immunofluorescent labelling of whole mount bladder tissue imaged with confocal microscope allowed localization of Ano1 and vimentin immunopositive cells. The effects of CaCC blockers: niflumic acid (NFA) (3,10,30 µM) and 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) (10, 30 µM) on spontaneous phasic contractile activity of intact (with mucosa) and denuded (without mucosa) detrusor strips were measured under isometric tension in organ baths (n = 141, N = 60).

Results

Ano1 expression was found at mRNA level in mucosa and detrusor layers. Confocal microscopy revealed presence of Ano1 immunopositive cells in mucosa and in detrusor layers; a subpopulation of vimentin positive cells expressed Ano1. Both chloride channel blockers reduced the amplitude and frequency of phasic contractions in denuded and intact strips.

Conclusions

Ano1 is expressed in rat urinary bladder and is present in cells sharing markers with interstitial cells. CaCC blockers reduced phasic activity of the bladder tissue. Ano1 is expressed in the bladder and plays a role in its spontaneous phasic contractile activity.     

Ectomycorrhizal and endophytic fungi associated with <Emphasis Type="Italic">Alnus glutinosa</Emphasis> growing in a saline area of central Poland

Alnus glutinosa (black alder) is a mycorrhizal pioneer tree species with tolerance to high concentrations of salt in the soil and can therefore be considered to be an important tree for the regeneration of forests areas devastated by excessive salt. However, there is still a lack of information about the ectomycorrhizal fungi (EMF) associated with mature individuals of A. glutinosa growing in natural saline conditions. The main objective of this study was to test the effect of soil salinity and other physicochemical parameters on root tips colonized by EMF, as well as on the species richness and diversity of an EMF community associated with A. glutinosa growing in natural conditions. We identified a significant effect of soil salinity (expressed as electrical conductivity: EC_e and EC_1:5) on fungal taxa but not on the total level of EM fungal colonization on roots. Increasing soil salinity promoted dark-coloured EMF belonging to the order Thelephorales (Tomentella sp. and Thelephora sp.). These fungi are also commonly found in soils polluted with heavy-metal. The ability of these fungi to grow in contaminated soil may be due to the presence of melanine, a natural dark pigment and common wall component of the Thelephoraceae that is known to act as a protective interface between fungal metabolism and biotic and abiotic environmental stressors. Moreover, increased colonization of fungi belonging to the class of Leotiomycetes and Sordiomycetes, known as endophytic fungal species, was observed at the test sites, that contained a larger content of total phosphorus. This observation confirms the ability of commonly known endophytic fungi to form ectomycorrhizal structures on the roots of A. glutinosa under saline stress conditions.