Nucleosome remodeler SNF2L suppresses cell proliferation and migration and attenuates Wnt signaling.

ISWI is an evolutionarily conserved ATPase that catalyzes nucleosome remodeling in different macromolecular complexes. Two mammalian ISWI orthologs, SNF2H and SNF2L, are thought to have specialized functions despite their high sequence similarity. To date, the function of SNF2L in human cells has not been a focus of research. Newly established specific monoclonal antibodies and selective RNA interference protocols have now enabled a comprehensive characterization of loss-of-function phenotypes in human cells. In contrast to earlier results, we found SNF2L to be broadly expressed in primary human tissues. Depletion of SNF2L in He La cells led to enhanced proliferation and increased migration. These phenomena were explained by transcriptome profiling, which identified SNF2L as a modulator of the Wnt signaling network. The cumulative effects of SNF2L depletion on gene expression portray the cell in a state of activated Wnt signaling characterized by increased proliferation and chemotactic locomotion. Accordingly, high levels of SNF2L expression in normal melanocytes contrast with undetectable expression in malignant melanoma. In summary, our data document an inverse relationship between SNF2L expression and features characteristic of malignant cells

Ionization energies of argon clusters: A combined experimental and theoretical study

We have measured appearance energies of Ar-n(+), n \u3c= 30, by electron impact of gas phase clusters. Quantum-chemical calculations have been performed to determine the adiabatic and vertical ionization energies of argon clusters up to n=4 and 6, respectively. The experimental appearance energy of the dimer ion approaches, under suitable cluster source conditions, the adiabatic ionization energy. The agreement with values obtained by photoionization and threshold photoelectron-photoion coincidence (TPEPICO) spectra demonstrates that autoionizing Rydberg states are accessible by electron impact. Appearance energies of larger clusters, though, exceed the TPEPICO values by about 0.5 eV. (c) 2005 American Institute of Physics

TERT Core Promotor Mutations In Early-Onset Bladder Cancer

Activating mutations in the core promoter of the TERT gene have been described in many different tumor entities. In vitro models showed a two- to fourfold increase in transcriptional activity of the TERT promoter through creation of a consensus binding motif for Ets/TCF transcription factors caused by these mutations. TERT core promoter mutations are the most common mutations in bladder cancer with a frequency between 55,6% and 82,8% described so far, and are independent of stage and grade. Since only few data on molecular alterations of early-onset bladder tumors exist, we assessed the frequency of TERT core promoter mutations in early-onset bladder cancer. Two cohorts of bladder tumors (early-onset patient group; n=144 (age of onset of disease ≤45 years); unselected, consecutive group; n=125) were examined for TERT core promoter mutations. After microdissection and extraction of DNA the corresponding hot-spot-regions in the TERT core promoter were examined by Sanger-sequencing or a SNaPshot approach. A significantly lower frequency of TERT core promoter mutations was found in tumors from the early-onset cohort compared to the consecutive cohort (57,6% vs. 84,8%, p<0,001). Among the early-onset cohort cases younger than the cohort’s median age of 39 years at disease onset showed a significant reduced number of TERT promoter mutations (31/67, 46,3%) than cases aged between 39 and 45 years (52/77, 67,5%; p=0,012). This association was not found in the consecutive cases. Mutation status was independent of tumor stage and grade. We conclude that in tumors from early-onset bladder cancer patients TERT core promoter mutations are not as frequent as in bladder tumors from consecutive cases, but seem to play an important role there as well. In patients below 39 years of age TERT core promoter mutations are a more infrequent event, suggesting different mechanisms of tumorigenesis in these young patients

Expression of cyclooxygenase-1 and cyclooxygenase-2 in human renal allograft rejection-- a prospective study

Cyclooxygenases (COX) are known to be involved in inflammatory kidney diseases. However, there are no data available about the expression of COX-1 and only preliminary reports about the expression of COX-2 in biopsies of patients undergoing acute renal allograft rejection. We conducted this prospective study to analyze the expression, distribution, and cellular localization of COX-1 and -2 and thus to elucidate the role of COX in human kidney transplantation. One hundred forty-four biopsies were included from patients without rejection and unaltered morphology (n = 60), with acute interstitial rejection (n = 7), with acute vascular rejection (n = 21), with chronic allograft nephropathy (n = 16), without rejection but with various other lesions (n = 40). COX-1 and -2 expression was localized in each biopsy by immunohistochemistry. We found a highly significant up-regulation of COX-1 in vessels and in infiltrating interstitial cells of patients with acute allograft rejection compared with biopsies with well-preserved tissue. Also, COX-2 expression was significantly elevated in infiltrating interstitial cells of biopsies with acute rejection. This is the first prospective study demonstrating a significant induction of both COX-1 and -2 in human allograft biopsies with acute rejection after renal transplantation