Abstract:
:Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a Zn-deficient diet reduces prostatic Zn levels (P = 0.025), increases cellular proliferation, and induces an inflammatory phenotype with COX-2 overexpression. This hyperplastic/inflammatory prostate has a human prostate cancer-like microRNA profile, with up-regulation of the Zn-homeostasis-regulating miR-183-96-182 cluster (fold change = 1.41-2.38; P = 0.029-0.0003) and down-regulation of the Zn importer ZIP1 (target of miR-182), leading to a reduction of prostatic Zn. This inverse relationship between miR-182 and ZIP1 also occurs in human prostate cancer tissue, which is known for Zn loss. The discovery that the Zn-depleted middle-aged rat prostate has a metabolic phenotype resembling that of human prostate cancer, with a 10-fold down-regulation of citric acid (P = 0.0003), links citrate reduction directly to prostatic Zn loss, providing the underlying mechanism linking dietary Zn deficiency with miR-183-96-182 overexpression, ZIP1 down-regulation, prostatic Zn loss, and the resultant citrate down-regulation, changes mimicking features of human prostate cancer. Thus, dietary Zn deficiency during rat middle age produces changes that mimic those of human prostate carcinoma and may increase the risk for prostate cancer, supporting the need for assessment of Zn supplementation in its prevention.
journal_name
Proc Natl Acad Sci U S Aauthors
Fong LY,Jing R,Smalley KJ,Wang ZX,Taccioli C,Fan S,Chen H,Alder H,Huebner K,Farber JL,Fiehn O,Croce CMdoi
10.1073/pnas.1813956115subject
Has Abstractpub_date
2018-11-20 00:00:00pages
E11091-E11100issue
47eissn
0027-8424issn
1091-6490pii
1813956115journal_volume
115pub_type
杂志文章abstract::Mutations induced by (+/-)trans-benzo-[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BaP-diol epoxide-1) were selected by using a recombinant plasmid vector system designed for the study of transcription termination signals. The plasmid contains a transcription terminator positioned between a promotor signal and the Escheric...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.11.6817
更新日期:1981-11-01 00:00:00
abstract::The attachment of human polymorphonuclear leukocytes (PMN) to bovine endothelial monolayers is increased by pretreatment of the endothelial cells with leukotriene B4 (LTB4). The response is dose dependent with a maximum at 10(-6) M, requires no more than 1 min of preincubation for the maximal effect, and decays linear...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.7.2191
更新日期:1984-04-01 00:00:00
abstract::The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1312296111
更新日期:2014-02-18 00:00:00
abstract::The role of spliced leader RNA (SL RNA) in trans-splicing in Caenorhabditis elegans has been studied through a combination of in vitro mutagenesis and in vivo complementation of rrs-1 mutant nematodes, which lack endogenous SL1 RNA. Three classes of mutant SL1 RNAs have been found-those that rescue the lethal phenotyp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.8.4235
更新日期:1998-04-14 00:00:00
abstract::Complementation of the plasmin fragments of reduced-carbamoylmethylated (Cam) human somatotropin (hGH) with those of reduced-carbamoylmethylated human chorionic somatomammotropin (hCS) have been investigated. It was found that the recombinant obtained by noncovalent interaction of [Cys(Cam)53]hGH-(1-134) with [Cys(Cam...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.4.1700
更新日期:1978-04-01 00:00:00
abstract::Emergence of antiestrogen-resistant cells in MCF-7 cells during suppression of estrogen signaling is a widely accepted model of acquired breast cancer resistance to endocrine therapy. To obtain insight into the genomic basis of endocrine therapy resistance, we characterized MCF-7 monoclonal sublines that survived 21-d...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0907560106
更新日期:2009-08-25 00:00:00
abstract::We have investigated the biochemical basis for negative regulation of interleukin 2 receptor alpha-chain (IL-2R alpha) gene expression. Transient transfection studies employing internally deleted forms of the IL-2R alpha promoter localized a negative regulatory element (NRE) between nucleotides -400 and -368 relative ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.21.8526
更新日期:1989-11-01 00:00:00
abstract::BSC-1 cells, epithelial cells of African green monkey kidney origin, show pronounced density-dependent regulation of growth in cell culture. Growth of the cells is rapid to a density of approximately 1.5 x 10(5) cells/per cm(2) in Dulbecco-modified Eagle's medium supplemented with 10% calf serum. Above this "saturatio...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.1.339
更新日期:1978-01-01 00:00:00
abstract::We have isolated RNA ligands with low-nanomolar affinity and high specificity to basic fibroblast growth factor from a pool of 10(14) molecules containing 30 randomized positions by the systematic evolution of ligands by exponential enrichment (SELEX) procedure. High-affinity ligands could be classified into two famil...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.23.11227
更新日期:1993-12-01 00:00:00
abstract::Over the last two decades, the number of gene/protein sequences gleaned from sequencing projects of individual genomes and environmental DNA has grown exponentially. Only a tiny fraction of these predicted proteins has been experimentally characterized, and the function of most proteins remains hypothetical or only pr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1815791116
更新日期:2019-03-26 00:00:00
abstract::ADP activates a family of cell surface receptors that modulate signaling pathways in a broad range of cells. ADP receptor antagonists are widely used to treat cardiovascular disease states. These studies identify a critical role for the stable reactive oxygen species hydrogen peroxide (H2O2) in mediating cellular resp...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1320854111
更新日期:2014-03-04 00:00:00
abstract::We have shown that cellular inhibitor of apoptosis proteins (cIAPs) impair clearance of hepatitis B virus (HBV) infection by preventing TNF-mediated killing/death of infected cells. A key question, with profound therapeutic implications, is whether this finding can be translated to the development of drugs that promot...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1502400112
更新日期:2015-05-05 00:00:00
abstract::Somatic cell hybridization of mouse erythroleukemia (MEL) cells and HEL cells, a human erythroleukemia line that produces fetal (gamma) but fails to express adult (beta) globin, was used to test whether the expression of the two human globin genes is regulated cis or trans. An experimental approach using anti-human gl...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.3.780
更新日期:1985-02-01 00:00:00
abstract::Expression of amino acid biosynthesis genes in bacteria is often repressed when abundant supplies of the cognate amino acid are available. Repression of the Bacillus subtilis lysC gene by lysine was previously shown to occur at the level of premature termination of transcription. In this study we show that lysine dire...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2133705100
更新日期:2003-10-14 00:00:00
abstract::In a search for a model cell system that might allow studies of the function of the Rho-related GTPase CDC42Hs in human cells, we measured the content and distribution of CDC42Hs in monocytes that were differentiating into macrophages. The total content of this protein increased 5- to 6-fold in phorbol ester-treated h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.10.4263
更新日期:1994-05-10 00:00:00
abstract::We have examined the use of our bis(sulfonamide) diol ligand (1) in the asymmetric addition of phenyl groups to cyclic alpha,beta-unsaturated ketones. Good to excellent enantioselectivities have been obtained with cyclic enones bearing alkyl substituents in the 2 position (71-97% enantiomeric excess). Furthermore, exc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0307119101
更新日期:2004-04-13 00:00:00
abstract::Agricultural foods and technologies are thought to have eased the mechanical demands of diet-how often or how hard one had to chew-in human populations worldwide. Some evidence suggests correspondingly worldwide changes in skull shape and form across the agricultural transition, although these changes have proved diff...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1702586114
更新日期:2017-08-22 00:00:00
abstract::Although the applicability of small subunit ribosomal RNA (16S rRNA) sequences for bacterial classification is now well accepted, the general use of these molecules has been hindered by the technical difficulty of obtaining their sequences. A protocol is described for rapidly generating large blocks of 16S rRNA sequen...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.20.6955
更新日期:1985-10-01 00:00:00
abstract::The natural history of follicular lymphoma (FL) is frequently characterized by transformation to a more aggressive diffuse large B cell lymphoma (DLBCL). We compared the gene-expression profiles between transformed DLBCL and their antecedent FL. No genes were observed to increase or decrease their expression in all of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.132253599
更新日期:2002-06-25 00:00:00
abstract::1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes parkinsonism in humans and nonhuman animals, and its use has led to greater understanding of the pathogenesis of Parkinson's disease. However, its molecular targets have not been defined. We show that mice lacking the gene for poly(ADP-rib...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.10.5774
更新日期:1999-05-11 00:00:00
abstract::Cumulative distributions of the number of doublings undergone by mixed megakaryocytic/erythroblastic colonies and by pure megakaryocytic colonies were determined from plasma clot cultures of bone marrow (from C57BL/6 mice) supplemented with erythropoietin. Analysis of these distributions suggests that these colonies a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.14.4410
更新日期:1982-07-01 00:00:00
abstract::Here, we report the isolation and characterization of an endogenous peptide ligand of GPR103 from rat brains. The purified peptide was found to be the 43-residue RF-amide peptide QRFP. We also describe two mouse homologues of human GPR103, termed mouse GPR103A and GPR103B. QRFP binds and activates the human GPR103, as...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0602371103
更新日期:2006-05-09 00:00:00
abstract::Electron micrographs are shown of the first component of human complement (C1) which has been crosslinked with a water-soluble carbodiimide to prevent dissociation into its C1q and C1r2C1s2 subunits. Two projections of the crosslinked molecule are seen in the electron micrographs, which are called "top" and "profile."...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.2.586
更新日期:1982-01-01 00:00:00
abstract::Schaftoside and isoschaftoside are bioactive natural products widely distributed in higher plants including cereal crops and medicinal herbs. Their biosynthesis may be related with plant defense. However, little is known on the glycosylation biosynthetic pathway of these flavonoid di-C-glycosides with different sugar ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2012745117
更新日期:2020-12-01 00:00:00
abstract::Little is known about stem cell biology or the specialized environments or niches believed to control stem cell renewal and differentiation in self-renewing tissues of the body. Functional assays for stem cells are available only for hematopoiesis and spermatogenesis, and the microenvironment, or niche, for hematopoie...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.111158198
更新日期:2001-05-22 00:00:00
abstract::The biconcave disk shape and deformability of mammalian RBCs rely on the membrane skeleton, a viscoelastic network of short, membrane-associated actin filaments (F-actin) cross-linked by long, flexible spectrin tetramers. Nonmuscle myosin II (NMII) motors exert force on diverse F-actin networks to control cell shapes,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1718285115
更新日期:2018-05-08 00:00:00
abstract::Quinate:NAD(+) 3-oxidoreductase (EC 1.1.1.24) from carrot cell suspension cultures has previously been shown to be activated by phosphorylation and inactivated by dephosphorylation. Here it is shown that the reactivation of the inactivated quinate:NAD(+) oxidoreductase is an enzyme-mediated process that requires ATP a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.17.5222
更新日期:1983-09-01 00:00:00
abstract::Bacillus thuringiensis subsp. kurstaki produces a proteinaceous crystalline inclusion that is toxic for lepidopteran larvae. There are several size classes of plasmids in this organism and the presence of one or more has been correlated with production of this protein, defined as a protoxin. DNA fragments of B. thurin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.79.19.6065
更新日期:1982-10-01 00:00:00
abstract::Cell-cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell-cell...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0808987105
更新日期:2008-10-28 00:00:00
abstract::beta 2-Glycoprotein I (beta 2-GPI), a phospholipid-binding plasma protein, is an absolute requirement (cofactor) for the binding of autoimmune-type anti-cardiolipin (aCL) antibodies to cardiolipin (CL). The nature of this cofactor activity and the specific regions of the molecule involved have not yet been determined....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.6.2141
更新日期:1993-03-15 00:00:00