Abstract:
:Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in solid tumors; however, currently, no reliable test for PI3K pathway activation exists for human tumors. Taking advantage of the observation that loss of PTEN, the negative regulator of PI3K, results in robust activation of this pathway, we developed and validated a microarray gene expression signature for immunohistochemistry (IHC)-detectable PTEN loss in breast cancer (BC). The most significant signature gene was PTEN itself, indicating that PTEN mRNA levels are the primary determinant of PTEN protein levels in BC. Some PTEN IHC-positive BCs exhibited the signature of PTEN loss, which was associated to moderately reduced PTEN mRNA levels cooperating with specific types of PIK3CA mutations and/or amplification of HER2. This demonstrates that the signature is more sensitive than PTEN IHC for identifying tumors with pathway activation. In independent data sets of breast, prostate, and bladder carcinoma, prediction of pathway activity by the signature correlated significantly to poor patient outcome. Stathmin, encoded by the signature gene STMN1, was an accurate IHC marker of the signature and had prognostic significance in BC. Stathmin was also pathway-pharmacodynamic in vitro and in vivo. Thus, the signature or its components such as stathmin may be clinically useful tests for stratification of patients for anti-PI3K pathway therapy and monitoring therapeutic efficacy. This study indicates that aberrant PI3K pathway signaling is strongly associated with metastasis and poor survival across carcinoma types, highlighting the enormous potential impact on patient survival that pathway inhibition could achieve.
journal_name
Proc Natl Acad Sci U S Aauthors
Saal LH,Johansson P,Holm K,Gruvberger-Saal SK,She QB,Maurer M,Koujak S,Ferrando AA,Malmström P,Memeo L,Isola J,Bendahl PO,Rosen N,Hibshoosh H,Ringnér M,Borg A,Parsons Rdoi
10.1073/pnas.0702507104subject
Has Abstractpub_date
2007-05-01 00:00:00pages
7564-9issue
18eissn
0027-8424issn
1091-6490pii
0702507104journal_volume
104pub_type
杂志文章abstract::A juvenile male zebra finch, Taeniopygia guttata, kept singly with its father develops a fairly complete imitation of the father's song. The imitation is less complete when other male siblings are present, possibly because as imitation commences, model abundance increases. Here we examine the consequences of allowing ...
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.96.22.12901
更新日期:1999-10-26 00:00:00
abstract::Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundan...
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.1105777108
更新日期:2011-08-23 00:00:00
abstract::Epstein-Barr virus infection in vitro immortalizes primary B cells. EBNA2 is an Epstein-Barr virus-encoded transcriptional transactivator that mimics the effects of activated Notch signaling and is essential for this proliferative response. An assay using Sindbis virus (SV) as a cell death inducer revealed that, like ...
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.182552499
更新日期:2002-09-03 00:00:00
abstract::Endocytic protein trafficking is directed by sorting signals on cargo molecules that are recognized by cytosolic adaptor proteins. However, the steps necessary to segregate the variety of cargoes during endocytosis remain poorly defined. Using Caenorhabditis elegans, we demonstrate that multiple plasma membrane endocy...
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.1302918110
更新日期:2013-07-16 00:00:00
abstract::An enzyme that catalyzes the conversion of bovine proinsulin to insulin has been purified from a bovine pancreatic extract. The product of conversion was identified as insulin by aminoacid analysis and determination of carboxyl terminal aminoacid residues. The purified enzyme preparation showed one major protein band ...
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.68.6.1312
更新日期:1971-06-01 00:00:00
abstract::The major small nuclear ribonucleoproteins (snRNPs) U1, U2, U4/U6, and U5 share a set of common proteins denoted B/B', D1, D2, D3, E, F, and G which play an important part in the biogenesis of the snRNPs. In addition, there is a link between the common proteins and autoimmunity; the three D proteins, together with B/B...
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.91.25.12317
更新日期:1994-12-06 00:00:00
abstract::Starting with assignments of proton nuclear magnetic resonance previously made for oxytocin in deuterated dimethylsulfoxide at 220 MHz, we have assigned resonances for the mammalian antidiuretic hormone, lysine vasopressin. The results demonstrate that spectral assignments of neurohypophyseal hormones and their congen...
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.69.7.1920
更新日期:1972-07-01 00:00:00
abstract::Cdc20/fizzy family proteins are involved in activation of the anaphase-promoting complex/cyclosome, which catalyzes the ubiquitin-dependent proteolysis of cell cycle regulatory proteins such as anaphase inhibitors and mitotic cyclins, leading to chromosome segregation and exit from mitosis. Previous work has shown tha...
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.96.13.7306
更新日期:1999-06-22 00:00:00
abstract::We previously demonstrated that the B chain of platelet-derived growth factor (PDGF-B) is transcribed in human atherosclerotic plaques, indicating that production of growth factors within plaques could occur during atherogenesis. However, since atherosclerotic plaques are composed of several cell types and three of th...
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.85.8.2810
更新日期:1988-04-01 00:00:00
abstract::In Caenorhabditis elegans, the small nuclear ribonucleoprotein (snRNP)-associated proteins U1A and U2B'' are approximately 50% identical to each other, and neither bears signature characteristics of mammalian U1A or U2B'' or the single Drosophila homolog, SNF. We show here that the genes that encode these proteins (rn...
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.0701720104
更新日期:2007-06-05 00:00:00
abstract::The active form of vitamin D, 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)2D], is synthesized from its precursor 25 hydroxyvitamin D [25(OH)D] via the catalytic action of the 25(OH)D-1alpha-hydroxylase [1alpha(OH)ase] enzyme. Many roles in cell growth and differentiation have been attributed to 1,25(OH)2D, including 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.131029498
更新日期:2001-06-19 00:00:00
abstract::In the present study the complete amino acid sequence of human plasma Zn-alpha 2-glycoprotein was determined. This protein whose biological function is unknown consists of a single polypeptide chain of 276 amino acid residues including 8 tryptophan residues and has a pyroglutamyl residue at the amino terminus. The loc...
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.85.3.679
更新日期:1988-02-01 00:00:00
abstract::In facultative photoperiodic flowering plants, noninductive photoperiods result in a delay in flowering, but such plants eventually flower, illustrating plasticity in an important developmental transition, flowering. The model plant, Arabidopsis, has a facultative photoperiod response. Although the inductive flowering...
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.1010834107
更新日期:2010-09-28 00:00:00
abstract::Albatrosses (Diomedeidae) do not occur in the North Atlantic Ocean today except as vagrants, although five species were present in the early Pliocene. No fossil breeding sites of albatrosses were known previously. The timing of extinction of albatrosses in the North Atlantic was likewise unknown. Deposits that formed ...
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.1934576100
更新日期:2003-10-28 00:00:00
abstract::Precise regulation of the evolutionarily conserved hypoxia-inducible transcription factor (HIF) ensures proper adaptation to variations in oxygen availability throughout development and into adulthood. Oxygen-dependent regulation of HIF stability and activity are mediated by hydroxylation of conserved proline and aspa...
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.202614999
更新日期:2002-11-26 00:00:00
abstract::The internal dynamics of bacteriorhodopsin, the light-driven proton pump in the purple membrane of Halobacterium halobium, has been studied by inelastic neutron scattering for various conditions of temperature and hydration. Light activation can take place when the membrane is vibrating harmonically. The ability of th...
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.90.20.9668
更新日期:1993-10-15 00:00:00
abstract::Double-positive (DP) thymocytes respond to intrathymic T-cell receptor (TCR) signals by undergoing positive selection and lineage differentiation into single-positive (SP) mature cells. Concomitant with these well-characterized events is the acquisition of a mature T-cell gene expression program characterized by the i...
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.1617669114
更新日期:2017-01-03 00:00:00
abstract::We present a full report of our enantioselective synthesis of (-)-longithorone A (1). The synthesis was designed to test the feasibility of the biosynthetic proposal for 1 put forward by Schmitz involving intermolecular and transannular Diels-Alder reactions of two [12]-paracyclophane quinones. We have found that if t...
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.0401952101
更新日期:2004-08-17 00:00:00
abstract::The structure and the expression of 11 cellular oncogenes (protooncogenes) were analyzed in primary cells from 20 acute lymphocytic (ALL) and 31 acute myelogenous (AML) leukemia patients. Neoplastic cells, obtained prior to initiation of therapy, were purified and classified, on the basis of both surface antigen patte...
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.83.12.4394
更新日期:1986-06-01 00:00:00
abstract::Previous studies have identified human breast tumor particles possessing many of the features characteristic of RNA tumor viruses. In addition to the expected size (600 S) and density (1.16 g/ml) these include possession of an outer membrane and an inner one surrounding a "core" containing a DNA polymerase and a large...
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.74.2.764
更新日期:1977-02-01 00:00:00
abstract::Direct conversion of carbon dioxide to multicarbon products remains as a grand challenge in electrochemical CO2 reduction. Various forms of oxidized copper have been demonstrated as electrocatalysts that still require large overpotentials. Here, we show that an ensemble of Cu nanoparticles (NPs) enables selective form...
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.1711493114
更新日期:2017-10-03 00:00:00
abstract::Vitamin A signals play critical roles during embryonic development. In particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor alpha (RXRalpha), as the systemic mutation of this receptor results in thinning of the myocardium and embryonic lethality. However, the molecular and c...
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.0504343102
更新日期:2005-12-20 00:00:00
abstract::T cell-dependent B-cell responses decline with age, suggesting defective CD4 T-cell function. CD4 memory T cells from individuals older than 65 y displayed increased and sustained transcription of the dual-specific phosphatase 4 (DUSP4) that shortened expression of CD40-ligand (CD40L) and inducible T-cell costimulator...
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.1109797109
更新日期:2012-04-10 00:00:00
abstract::Twelve zeolitic imidazolate frameworks (ZIFs; termed ZIF-1 to -12) have been synthesized as crystals by copolymerization of either Zn(II) (ZIF-1 to -4, -6 to -8, and -10 to -11) or Co(II) (ZIF-9 and -12) with imidazolate-type links. The ZIF crystal structures are based on the nets of seven distinct aluminosilicate zeo...
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.0602439103
更新日期:2006-07-05 00:00:00
abstract::Isolation and chromatography of collagen from chick cartilage revealed an excess of alpha1 relative to alpha2-chains. Characterization of the cyanogen bromide peptides from the alpha1 fraction indicated the presence of two homologous forms of alpha1. The results suggest that cartilage contains two collagens, one ident...
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.64.4.1264
更新日期:1969-12-01 00:00:00
abstract::In eukaryotes, ubiquitination is an important posttranslational process achieved through a cascade of ubiquitin-activating (E1), conjugating (E2), and ligase (E3) enzymes. Many pathogenic bacteria deliver virulence factors into the host cell that function as E3 ligases. How these bacterial "Trojan horses" integrate in...
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.1115025109
更新日期:2012-02-07 00:00:00
abstract::We examine a nonreciprocally coupled dynamical model of a mixture of two diffusing species. We demonstrate that nonreciprocity, which is encoded in the model via antagonistic cross-diffusivities, provides a generic mechanism for the emergence of traveling patterns in purely diffusive systems with conservative dynamics...
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.2010318117
更新日期:2020-08-18 00:00:00
abstract::Glutamyl-tRNA (Glu-tRNA), formed by Glu-tRNA synthetase (GluRS), is a substrate for protein biosynthesis and tetrapyrrole formation by the C(5) pathway. In this route Glu-tRNA is transformed to delta-aminolevulinic acid, the universal precursor of tetrapyrroles (e.g., heme and chlorophyll) by the action of Glu-tRNA re...
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.0611611104
更新日期:2007-02-27 00:00:00
abstract::Rapid development of genetic variability may contribute to the pathogenicity of lentiviruses as it may allow escape from immune surveillance and/or from suppression of virus replication. Although apathogenic in African green monkeys, simian immunodeficiency virus isolated from African green monkeys is shown to display...
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.88.18.8126
更新日期:1991-09-15 00:00:00
abstract::Photoreceptors of the Xenopus laevis retina are the site of a circadian clock. As part of a differential display screen for rhythmic gene products in this system, we have identified a photoreceptor-specific mRNA expressed in peak abundance at night. cDNA cloning revealed an open reading frame encoding a putative 388 a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 评论,杂志文章
doi:10.1073/pnas.93.25.14884
更新日期:1996-12-10 00:00:00