Abstract：
:Understanding the pathways that control epithelial carcinogenesis is vital to the development of effective treatments. The Polycomb group family member Bmi1 is overexpressed in numerous epithelial tumors, but its role in their development has not been established. We now show a key role for Bmi1 in lung adenocarcinoma. Whereas lung development occurs normally in Bmi1-deficient mice, loss of Bmi1 decreases the number and progression of lung tumors at a very early point in an oncogenic K-ras-initiated mouse model of lung cancer. This correlates with a defect in the ability of Bmi1-deficient putative bronchiolalveolar stem cells (BASCs) to proliferate in response to the oncogenic stimulus. Notably, in the absence of oncogenic K-ras, Bmi1-deficient BASCs show impaired proliferation and self-renewal capacity in culture and after lung injury in vivo. Abrogated lung cancer development and BASC self-renewal occur partially in a p19(ARF)-dependent manner. Our data suggest that Bmi1 deficiency suppresses tumor development by limiting the expansion potential of BASCs, the apparent lung cancer cells of origin. Because Bmi1 is elevated in additional tumor types, this suggests that Bmi1 plays a key role in regulating proliferation of both stem cells and tumor cells in diverse adult epithelial tissues.
journal_name
Proc Natl Acad Sci U S Aauthors
Dovey JS,Zacharek SJ,Kim CF,Lees JAdoi
10.1073/pnas.0803574105subject
Has Abstractpub_date
2008-08-19 00:00:00pages
11857-62issue
33eissn
0027-8424issn
1091-6490pii
0803574105journal_volume
105pub_type
杂志文章abstract：:Efficient execution of perceptual-motor tasks requires rapid voluntary reconfiguration of cognitive task sets as circumstances unfold. Such acts of cognitive control, which are thought to rely on a network of cortical regions in prefrontal and posterior parietal cortex, include voluntary shifts of attention among perc...
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.0903593106
更新日期：2009-10-20 00:00:00
abstract：:Environmental cues are transmitted to the interior of the cell via a complex network of signaling hubs. Receptor tyrosine kinases (RTKs) and trimeric G proteins are two such major signaling hubs in eukaryotes. Conventionally, canonical signal transduction via trimeric G proteins is thought to be triggered exclusively ...
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.1420140112
更新日期：2015-03-03 00:00:00
abstract：:In contrast with speciation in terrestrial organisms, marine plankton frequently display gradual morphological change without lineage division (e.g., phyletic gradualism or gradual evolution), which has raised the possibility that a different mode of evolution dominates within pelagic environments. Here, we reexamine ...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 历史文章,杂志文章
doi：10.1073/pnas.0902887106
更新日期：2009-12-15 00:00:00
abstract：:Many bacteria use N-acyl homoserine lactone (AHL) signals to coordinate the behavior of individual cells in a local population. The successful infection of eukaryotic hosts by bacteria seems to depend particularly on such AHL-mediated "quorum-sensing" regulation. We have used proteome analysis to show that a eukaryoti...
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.262672599
更新日期：2003-02-04 00:00:00
abstract：:Inbred Lewis (LEW/N) female rats develop an arthritis in response to group A streptococcal cell wall peptidoglycan polysaccharide (SCW), which mimics human rheumatoid arthritis. Histocompatible Fischer (F344/N) rats do not develop arthritis in response to the same SCW stimulus. To evaluate this difference in inflammat...
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.86.7.2374
更新日期：1989-04-01 00:00:00
abstract：:Receptors for platelet-derived growth factor (PDGF) have previously only been found on cells of mesenchymal and glial origin. This study shows PDGF receptors on an anaplastic thyroid carcinoma cell line, C 643, that was found to express thyroglobulin mRNA, confirming its origin from thyroid epithelium. Northern blot 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.85.23.9302
更新日期：1988-12-01 00:00:00
abstract：:Landscape-scale reconstructions of ancient environments within the cradle of humanity may reveal insights into the relationship between early hominins and the changing resources around them. Many studies of Olduvai Gorge during Pliocene-Pleistocene times have revealed the presence of precession-driven wet-dry cycles 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.2004532117
更新日期：2020-10-06 00:00:00
abstract：:The density of benzodiazepine/gamma-aminobutyric acid receptor binding sites was lower in the midbrain of seizure-susceptible gerbils compared to control seizure-resistant gerbils. Binding of [3H]diazepam to high-affinity brain-specific sites in membrane homogenates of gerbil brain showed a 20-30% lower binding in mid...
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.82.19.6701
更新日期：1985-10-01 00:00:00
abstract：:August-Copenhagen-Irish (ACI) rats are unique in that the ovary-intact females develop high incidence of mammary cancers induced solely by hormones upon prolonged exposure to high levels of estrogen alone. Studies have also shown that such prolonged exposure to high-dose estrogen results in human-like aneuploid mammar...
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.0710535105
更新日期：2008-03-04 00:00:00
abstract：:A recent major conceptual advance has been the recognition of the importance of immune system-neuronal interactions in the modulation of brain function, one example of which is spinal pain processing in neuropathic states. Here, we report that in peripheral nerve-injured rats, the lysosomal cysteine protease cathepsin...
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.0610811104
更新日期：2007-06-19 00:00:00
abstract：:Citrus bacterial canker (CBC) caused by Xanthomonas axonopodis pv. citri (Xac) was first documented in India and Java in the mid 19th century. Since that time, the known distribution of the disease has steadily increased. Concurrent with the dispersion of the pathogen, the diversity of described strains continues to 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.0705590104
更新日期：2007-11-20 00:00:00
abstract：:Single-cell RNA sequencing (scRNA-seq) enables the quantification of each gene's expression distribution across cells, thus allowing the assessment of the dispersion, nonzero fraction, and other aspects of its distribution beyond the mean. These statistical characterizations of the gene expression distribution are cri...
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.1721085115
更新日期：2018-07-10 00:00:00
abstract：:A cDNA clone that hybridizes to an mRNA (1A10) that accumulates to a substantial level in the axis of the germinating soybean seed was sequenced. The amino acid sequence of the clone indicates an almost perfect repeat of Pro-Pro-Val-Tyr-Lys resulting in a protein containing 40% proline and lacking serine and histidine...
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.85.4.1082
更新日期：1988-02-01 00:00:00
abstract：:Barttin is an accessory subunit of a subgroup of ClC-type chloride channels expressed in renal and inner ear epithelia. In this study, we examined the effects of barttin on two ClC-K channel isoforms, rat ClC-K1 and human ClC-Kb, using heterologous expression, patch clamping, confocal imaging, and flow cytometry. In 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.0601631103
更新日期：2006-07-25 00:00:00
abstract：:We demonstrate that the receptor binding moiety of Escherichia coli heat-labile enterotoxin (EtxB) can completely prevent autoimmune disease in a murine model of arthritis. Injection of male DBA/1 mice at the base of the tail with type II collagen in the presence of complete Freund's adjuvant normally leads to arthrit...
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.94.10.5290
更新日期：1997-05-13 00:00:00
abstract：:Topographic sensory maps are a prominent feature of the adult primate brain. Here, we asked whether topographic representations of the body are present at birth. Using functional MRI (fMRI), we find that the newborn somatomotor system, spanning frontoparietal cortex and subcortex, comprises multiple topographic repres...
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.1912636116
更新日期：2019-12-03 00:00:00
abstract：:A recently described organ culture system for human thymocytes is shown to support the generation of a diverse T-cell receptor repertoire in vitro: thymocytes of the alpha beta lineage, including representatives of the V beta families 5.2/5.3, 6.7, and 8, accounted for the majority of T-cell receptor-positive cells 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.89.10.4255
更新日期：1992-05-15 00:00:00
abstract：:Conflicts of interest between the community and its members are at the core of human social dilemmas. If observed selfishness has future costs, individuals may hide selfish acts but display altruistic ones, and peers aim at identifying the most selfish persons to avoid them as future social partners. An interaction 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.1108996108
更新日期：2011-11-08 00:00:00
abstract：:DNA from phi X174 is replicated in vitro with a fidelity similar to that found genetically. A mutation of TAG leads to TGG may be induced, however, by varying the concentrations of deoxynucleoside triphosphates, with a frequency proportional to [dGTP]2/[dATP]. This complex concentration dependence is consistent with 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.76.10.4946
更新日期：1979-10-01 00:00:00
abstract：:Psychopathy is associated with persistent antisocial behavior and a striking lack of regret for the consequences of that behavior. Although explanatory models for psychopathy have largely focused on deficits in affective responsiveness, recent work indicates that aberrant value-based decision making may also play a ro...
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.1609985113
更新日期：2016-12-13 00:00:00
abstract：:Many important hominid-bearing fossil localities in East Africa are in regions that are extremely hot and dry. Although humans are well adapted to such conditions, it has been inferred that East African environments were cooler or more wooded during the Pliocene and Pleistocene when this region was a central stage 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.1001824107
更新日期：2010-06-22 00:00:00
abstract：:Activator protein-1 (AP-1) is a crucial transcription factor implicated in numerous cancers. For this reason, nine homologues of the AP-1 leucine zipper region have been characterized: Fos (c-Fos, FosB, Fra1, and Fra2), Jun (c-Jun, JunB, and JunD), and semirational library-designed winning peptides FosW and JunW. The ...
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.0509880103
更新日期：2006-06-13 00:00:00
abstract：:It is generally believed that the old quantum theory, as presented by Niels Bohr in 1913, fails when applied to few electron systems, such as the H(2) molecule. Here, we find previously undescribed solutions within the Bohr theory that describe the potential energy curve for the lowest singlet and triplet states of 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.0505778102
更新日期：2005-08-23 00:00:00
abstract：:The timing of human colonization of East Polynesia, a vast area lying between Hawai'i, Rapa Nui, and New Zealand, is much debated and the underlying causes of this great migration have been enigmatic. Our study generates evidence for human dispersal into eastern Polynesia from islands to the west from around AD 900 an...
journal_title：Proceedings of the National Academy of Sciences of the United States of America
pub_type： 历史文章,杂志文章
doi：10.1073/pnas.1920975117
更新日期：2020-04-21 00:00:00
abstract：:Binding of a partial proteolytic digest by V8 enzyme of the yeast site-specific recombinase Flp to its target site gives rise to DNA-protein complexes that are smaller than those produced by the full-sized protein. The smallest of these complexes (occupancy of one peptide monomer per site) contains either one of two p...
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.88.14.5944
更新日期：1991-07-15 00:00:00
abstract：:The origin recognition complex (ORC) binds sites from which DNA replication is initiated. We address ORC binding selectivity in vivo by mapping ∼52,000 ORC2 binding sites throughout the human genome. The ORC binding profile is broader than those of sequence-specific transcription factors, suggesting that ORC is not bo...
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.1609060113
更新日期：2016-08-16 00:00:00
abstract：:A tremendous amount of radioactivity was discharged because of the damage to cooling systems of nuclear reactors in the Fukushima No. 1 nuclear power plant in March 2011. Fukushima and its adjacent prefectures were contaminated with fission products from the accident. Here, we show a geographical distribution of radio...
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.1111724108
更新日期：2011-12-06 00:00:00
abstract：:Foreign DNA molecules and chromosomal fragments are generally eliminated from proliferating cells, but we know little about how mammalian cells prevent their propagation. Here, we show that dividing human and canine cells partition transfected plasmid DNA asymmetrically, preferentially into the daughter cell harboring...
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.1606091113
更新日期：2016-06-28 00:00:00
abstract：:Current evidence suggests that the length of poly(A) tails of bacterial mRNAs result from a competition between poly(A) polymerase and exoribonucleases that attack the 3' ends of RNAs. Here, we show that host factor Hfq is also involved in poly(A) tail metabolism. Inactivation of the hfq gene reduces the length of pol...
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.040549897
更新日期：2000-02-15 00:00:00
abstract：:The Escherichia coli strain, ts-rnp5, originally described in 1975 by G. D. Burdick and H. Berger, is shown to possess an RNA polymerase (RNA nucleotidyltransferase) sigma subunit with an activity 4--6 times less thermostable at 45 degrees than sigma from wild-type strains. This defect remains associated with the sigm...
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.75.1.427
更新日期：1978-01-01 00:00:00
