Characterization of glycine-N-acyltransferase like 1 (GLYATL1) in prostate cancer

BackgroundRecent microarray and sequencing studies of prostate cancer showed multiple molecular alterations during cancer progression. It is critical to evaluate these molecular changes to identify new biomarkers and targets. We performed analysis of glycine-N-acyltransferase like 1 (GLYATL1) expression in various stages of prostate cancer in this study and evaluated the regulation of GLYATL1 by androgen.MethodWe performed in silico analysis of cancer gene expression profiling and transcriptome sequencing to evaluate GLYATL1 expression in prostate cancer. Furthermore, we performed immunohistochemistry using specific GLYATL1 antibody using high-density prostate cancer tissue microarray containing primary and metastatic prostate cancer. We also tested the regulation of GLYATL1 expression by androgen and ETS transcription factor ETV1. In addition, we performed RNA-sequencing of GLYATL1 modulated prostate cancer cells to evaluate the gene expression and changes in molecular pathways.ResultsOur in silico analysis of cancer gene expression profiling and transcriptome sequencing we revealed an overexpression of GLYATL1 in primary prostate cancer. Confirming these findings by immunohistochemistry, we show that GLYATL1 is overexpressed in primary prostate cancer compared with metastatic prostate cancer and benign prostatic tissue. Low-grade cancers had higher GLYATL1 expression compared to high-grade prostate tumors. Our studies showed that GLYATL1 is upregulated upon androgen treatment in LNCaP prostate cancer cells which harbors ETV1 gene rearrangement. Furthermore, ETV1 knockdown in LNCaP cells showed downregulation of GLYATL1 suggesting potential regulation of GLYATL1 by ETS transcription factor ETV1. Transcriptome sequencing using the GLYATL1 knockdown prostate cancer cell lines LNCaP showed regulation of multiple metabolic pathways.ConclusionsIn summary, our study characterizes the expression of GLYATL1 in prostate cancer and explores the regulation of its regulation in prostate cancer showing role for androgen and ETS transcription factor ETV1. Future studies are needed to decipher the biological significance of these findings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151252/1/pros23887.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151252/2/pros23887_am.pd

Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression

Multiple, complex molecular events characterize cancer development and progression(1,2). Deciphering the molecular networks that distinguish organ- confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high- throughput liquid- and- gas- chromatography- based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer ( 42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N- methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non- invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine- N- methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.Early Detection Research Network ; National Institutes of Health ; MTTC ; Clinical Translational Science Award ; Fund for Discovery of the University of Michigan Comprehensive Cancer Center ; University of Michigan Cancer Biostatistics Training Grant ; Doris Duke Charitable FoundationWe thank J. Granger for help in manuscript preparation, J. Siddiqui and R. Varambally for help with the clinical database, and A. Vellaichamy and S. Pullela for technical assistance. We thank K. Pienta for access to metastatic prostate cancer samples from the University of Michigan Prostate SPORE rapid autopsy programme. This work is supported in part by the Early Detection Research Network (A.M.C., J.T.W.), National Institutes of Health (A.S., S.P., J.B., T.M.R., D.G., G.S.O. and A.M.C.) and an MTTC grant (G.S.O. and A.S.). A.M.C. is supported by a Clinical Translational Science Award from the Burroughs Welcome Foundation. A. S. is supported by a grant from the Fund for Discovery of the University of Michigan Comprehensive Cancer Center. L. M. P. is supported by the University of Michigan Cancer Biostatistics Training Grant. A. M. C and S. P. are supported by the Doris Duke Charitable Foundation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62661/1/nature07762.pd

Ferritin Light Chain Confers Protection Against Sepsis-Induced Inflammation and Organ Injury

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Expression and role of PAICS, a de novo purine biosynthetic gene in prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143605/1/pros23533_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143605/2/pros23533.pd

Crystallographic data on axially compressed Kevlar 49 fibres

Axially compressed Kevlar 49 fibres have been examined by X-ray diffraction methods. The most prominent effect of axial compression is the anisotropic deformation of the unit cell. Whereas the c-axial length, which corresponds to the chain axis, undergoes contraction, the basal plane dimensions manifest enlargement. The deformations increase with the extent of axial compression. The half-widths and the azimuthal spread of reflections also exhibit changes. The compression induced structural changes provide qualitative support to the experimentally observed reduction in tensile strength and modulus

Low temperature crystallographic data on Kevlar 49 fibres

Using X-ray diffraction data, the behaviour of Kevlar49 fibres at lowtemperatures, up to -100xB0;C, has been analysed. During cooling, the basal plane of the monoclinic unit cell13; shrinks whereas the c- (unique, chain axis) length is not significantly affected. In contrast, in the return heating cycle to ambient temperature, the basal plane expands and contraction occurs along the chain direction. The unit cell registers a reduction in volume in both the cooling and heating cycles. Conspicuously,after a cycle of cooling and heating, the unit cell does not return to its initial volume

Phase transitions in triammonium hydrogen disulphate. Crystal structures at -110° c and 140° c

Structural phase transitions in triammonium hydrogen disulphate have been characterised by determining the crystaI structures at -110°C by single crystal X-ray diffraction studies and at +140°C by X-ray powder diffraction studies. The structure at -110°C is monoclinic C2/c (a=15.578(4), b=5.816(1), c=10.050(4) Å, β= 101.58(3)° and volume= 892.0(4) Å3), whereas the structure at the higher temperature (+140°C) is rhombohedral R3m (a=5.906(1), c=22.602(1) Å, volume = 682.75 Å3 and Z=3). The starting model for Rietveld refinement was derived from that of the corresponding selenium analogue. The effect of reorientation of SO4 groups in terms of intra and intermolecular interactions is analysed

Mechanistics of stabilisation via doping in bismuthsesquioxide (Bi2-2xHo2xO3; x=0.2) - A combined approach of Rietveld and microstructural analysis

delta-Bi1.6Ho0.4O3, is cubic, Fm3m, with a=5.5291(5) Angstrom, V=169.03(3) Angstrom(3), D-calc=8.838 g/cm(3), D-measured (powder technique)=8.607 g/cm(3), with Z=2. Rietveld profile refinements on high resolution X-ray diffraction data give R-p=0.143, R-wp=0.188, R-(I,R-HKL)=0.090, R-(expected)=0.078 confirming the earlier results on the structure of this phase to have a fluorite type lattice with highly disordered oxygen sublattice. Strain and crystal size analysis of all the reflections in the range (2 theta=5-100.94 degrees) from holmium doped bismuth sesquioxide were carried out and compared with the results of the simulated whole powder pattern of Bi2O3 for alpha and delta phases. These results provide pointers to the possible mechanism of stabilization of delta phase on holmium substitution