Suppression of tumor growth by senescence in virally transformed human fibroblasts.

Abstract:

:Normal human cells whether embryonic, neonatal, or adult are resistant to experimentally induced tumorigenesis in contrast to rodent or chicken cells. We showed previously that neither transformation with simian virus 40 DNA nor transfection with human mutant HRAS DNA immortalized FS-2 cells (diploid, neonatal human fibroblasts). Further, tumorigenicity was not induced, despite expression of the respective transforming gene products tumor (T) antigen or p21. Here we describe treatment of FS-2 and FSSV cells with baboon endogenous virus pseudotyped Kirsten murine sarcoma virus. FSSV cells were derived from individual foci of simian virus 40-transformed FS-2 cells. The retrovirus-treated FS-2 cells (called FSK) appeared heavily granulated and expressed viral p21 but senesced during passage in culture and were not tumorigenic. The retrovirus-treated FSSV-27 cells (called FSVK-27) expressed simian virus 40 tumor antigen, had elevated levels of viral p21 protein, and formed transient tumors in nude mice. Whether grown in culture or explanted from small tumors, the FSVK-27 cells senesced. The FSVK-46 cells senesced before tumor growth occurred. On the contrary, Kirsten murine sarcoma virus (baboon endogenous virus) treatment of immortalized nontumorigenic human fibroblasts expressing simian virus 40 tumor antigen (Va2 cells) led to consistent tumor formation. The results illustrate the importance of senescence in restricting the tumor-forming ability of human cells.

authors

O'Brien W,Stenman G,Sager R

doi

10.1073/pnas.83.22.8659

subject

Has Abstract

pub_date

1986-11-01 00:00:00

pages

8659-63

issue

22

eissn

0027-8424

issn

1091-6490

journal_volume

83

pub_type

杂志文章
  • (2'-5')Oligoadenylate in rat liver: modulation after partial hepatectomy.

    abstract::(2'-5')Oligoadenylate synthetase [(2'-5')A synthetase], which synthesizes a series of oligoadenylates ppp-(A2'p)n5'A [collectively referred to as (2'-5')A], has been described previously in rat liver cells, where its concentration varied with the growth status of this organ--i.e., it decreased during the early phase o...

    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.80.15.4609

    authors: Etienne-Smekens M,Vandenbussche P,Content J,Dumont JE

    更新日期:1983-08-01 00:00:00

  • alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies.

    abstract::Lewy bodies and Lewy neurites are the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies. They are made of abnormal filamentous assemblies of unknown composition. We show here that Lewy bodies and Lewy neurites from Parkinson's disease and dementia with Lewy bodies are stai...

    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.95.11.6469

    authors: Spillantini MG,Crowther RA,Jakes R,Hasegawa M,Goedert M

    更新日期:1998-05-26 00:00:00

  • The vertical occipital fasciculus: a century of controversy resolved by in vivo measurements.

    abstract::The vertical occipital fasciculus (VOF) is the only major fiber bundle connecting dorsolateral and ventrolateral visual cortex. Only a handful of studies have examined the anatomy of the VOF or its role in cognition in the living human brain. Here, we trace the contentious history of the VOF, beginning with its origin...

    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.1418503111

    authors: Yeatman JD,Weiner KS,Pestilli F,Rokem A,Mezer A,Wandell BA

    更新日期:2014-12-02 00:00:00

  • Dynein pulls microtubules without rotating its stalk.

    abstract::Dynein is a microtubule motor that powers motility of cilia and flagella. There is evidence that the relative sliding of the doublet microtubules is due to a conformational change in the motor domain that moves a microtubule bound to the end of an extension known as the stalk. A predominant model for the movement invo...

    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.0808194105

    authors: Ueno H,Yasunaga T,Shingyoji C,Hirose K

    更新日期:2008-12-16 00:00:00

  • Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter.

    abstract::Presynaptic and postsynaptic differentiation occurs at axodendritic contacts between CNS neurons. Synaptic adhesion mediated by synaptic cell adhesion molecule (SynCAM) and beta-neurexins/neuroligins triggers presynaptic differentiation. The signals that trigger postsynaptic differentiation are, however, unknown. Here...

    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.0502038102

    authors: Nam CI,Chen L

    更新日期:2005-04-26 00:00:00

  • Inhibition of induced aldosterone biosynthesis with a specific antagonist of angiotensin II.

    abstract::The present study determined the effect of [Sar(1)-Ile(8)]-angiotensin II on steroidogenesis and induced aldosterone synthesis by the octapeptide angiotensin II, the heptapeptide des-Asp(1)-angiotensin II, and adrenocorticotropic hormone. Rabbit adrenal cells were suspended by incubation of the capsular cortical tissu...

    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.71.2.341

    authors: Chiu AT,Peach MJ

    更新日期:1974-02-01 00:00:00

  • The nuclear factor of activated T cells in pulmonary arterial hypertension can be therapeutically targeted.

    abstract::In pulmonary arterial hypertension (PAH), antiapoptotic, proliferative, and inflammatory diatheses converge to create an obstructive vasculopathy. A selective down-regulation of the Kv channel Kv1.5 has been described in human and animal PAH. The resultant increase in intracellular free Ca(2+) ([Ca(2+)](i)) and K(+) (...

    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.0610467104

    authors: Bonnet S,Rochefort G,Sutendra G,Archer SL,Haromy A,Webster L,Hashimoto K,Bonnet SN,Michelakis ED

    更新日期:2007-07-03 00:00:00

  • N-Methylprotoporphyrin IX: chemical synthesis and identification as the green pigment produced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine treatment.

    abstract::The hepatic pigment accumulated in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated rats, which has been reported to inhibit ferrochelatase, has been isolated and purified. The pigment has been resolved into one major, one minor, and two trace components, all of which appear to be isomeric porphyrins. The major fract...

    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.78.3.1490

    authors: Ortiz de Montellano PR,Beilan HS,Kunze KL

    更新日期:1981-03-01 00:00:00

  • Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine.

    abstract::An isoform of the mammalian renal type II Na/Pi-cotransporter is described. Homology of this isoform to described mammalian and nonmammalian type II cotransporters is between 57 and 75%. Based on major diversities at the C terminus, the new isoform is designed as type IIb Na/Pi-cotransporter. Na/Pi-cotransport mediate...

    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.95.24.14564

    authors: Hilfiker H,Hattenhauer O,Traebert M,Forster I,Murer H,Biber J

    更新日期:1998-11-24 00:00:00

  • Gain of chromosome band 7q11 in papillary thyroid carcinomas of young patients is associated with exposure to low-dose irradiation.

    abstract::The main consequence of the Chernobyl accident has been an increase in papillary thyroid carcinomas (PTCs) in those exposed to radioactive fallout as young children. Our aim was to identify genomic alterations that are associated with exposure to radiation. We used array comparative genomic hybridization to analyze 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.1017137108

    authors: Hess J,Thomas G,Braselmann H,Bauer V,Bogdanova T,Wienberg J,Zitzelsberger H,Unger K

    更新日期:2011-06-07 00:00:00

  • Potent inhibition of scrapie prion replication in cultured cells by bis-acridines.

    abstract::Prion diseases are characterized by an accumulation of PrP(Sc), a misfolded isoform of the normal cellular prion protein, PrP(C). We previously reported the bioactivity of acridine-based compounds against PrP(Sc) replication in scrapie-infected neuroblastoma cells and now report the improved potency of bis-acridine co...

    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.2627988100

    authors: May BC,Fafarman AT,Hong SB,Rogers M,Deady LW,Prusiner SB,Cohen FE

    更新日期:2003-03-18 00:00:00

  • Snapshots of a protein folding intermediate.

    abstract::We have investigated the folding dynamics of Thermus thermophilus cytochrome c(552) by time-resolved fluorescence energy transfer between the heme and each of seven site-specific fluorescent probes. We have found both an equilibrium unfolding intermediate and a distinct refolding intermediate from kinetics studies. De...

    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.1221832110

    authors: Yamada S,Bouley Ford ND,Keller GE,Ford WC,Gray HB,Winkler JR

    更新日期:2013-01-29 00:00:00

  • Mixed-power scaling of whole-plant respiration from seedlings to giant trees.

    abstract::The scaling of respiratory metabolism with body mass is one of the most pervasive phenomena in biology. Using a single allometric equation to characterize empirical scaling relationships and to evaluate alternative hypotheses about mechanisms has been controversial. We developed a method to directly measure respiratio...

    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.0902554107

    authors: Mori S,Yamaji K,Ishida A,Prokushkin SG,Masyagina OV,Hagihara A,Hoque AT,Suwa R,Osawa A,Nishizono T,Ueda T,Kinjo M,Miyagi T,Kajimoto T,Koike T,Matsuura Y,Toma T,Zyryanova OA,Abaimov AP,Awaya Y,Araki MG,Kawasaki T

    更新日期:2010-01-26 00:00:00

  • Two distinctly regulated events, priming and triggering, during retinoid-induced maturation and resistance of NB4 promyelocytic leukemia cell line.

    abstract::In t(15;17) acute promyelocytic leukemia, all-trans retinoic acid (RA) induces leukemic cell maturation in vitro and remission in acute promyelocytic leukemia patients, but in vivo treatments invariably lead to relapse with resistance to RA. NB4, a maturation-inducible cell line, and NB4-RAr sublines (R1 and R2) displ...

    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.91.18.8428

    authors: Ruchaud S,Duprez E,Gendron MC,Houge G,Genieser HG,Jastorff B,Doskeland SO,Lanotte M

    更新日期:1994-08-30 00:00:00

  • Intrinsic expression of viperin regulates thermogenesis in adipose tissues.

    abstract::Viperin is an interferon (IFN)-inducible multifunctional protein. Recent evidence from high-throughput analyses indicates that most IFN-inducible proteins, including viperin, are intrinsically expressed in specific tissues; however, the respective intrinsic functions are unknown. Here we show that the intrinsic expres...

    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.1904480116

    authors: Eom J,Kim JJ,Yoon SG,Jeong H,Son S,Lee JB,Yoo J,Seo HJ,Cho Y,Kim KS,Choi KM,Kim IY,Lee HY,Nam KT,Cresswell P,Seong JK,Seo JY

    更新日期:2019-08-27 00:00:00

  • Degassing of reduced carbon from planetary basalts.

    abstract::Degassing of planetary interiors through surface volcanism plays an important role in the evolution of planetary bodies and atmospheres. On Earth, carbon dioxide and water are the primary volatile species in magmas. However, little is known about the speciation and degassing of carbon in magmas formed on other planets...

    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.1219266110

    authors: Wetzel DT,Rutherford MJ,Jacobsen SD,Hauri EH,Saal AE

    更新日期:2013-05-14 00:00:00

  • Isolation of a cytokinin gene, ZOG1, encoding zeatin O-glucosyltransferase from Phaseolus lunatus.

    abstract::Zeatin is the most active and ubiquitous of the naturally occurring cytokinins. The O-glucoside of zeatin, found in all plants examined, is considered to be important in cytokinin transport, storage, and protection against cytokinin oxidases. The enzyme UDPglucose:zeatin O-glucosyltransferase (EC 2.4.1.203) was previo...

    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.96.1.284

    authors: Martin RC,Mok MC,Mok DW

    更新日期:1999-01-05 00:00:00

  • CD93 negatively regulates astrogenesis in response to MMRN2 through the transcriptional repressor ZFP503 in the developing brain.

    abstract::Astrogenesis is repressed in the early embryonic period and occurs in the late embryonic period. A variety of external and internal signals contribute to the sequential differentiation of neural stem cells. Here, we discovered that immune-related CD93 plays a critical negative role in the regulation of astrogenesis 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.1922713117

    authors: Liang Q,Su L,Zhang D,Jiao J

    更新日期:2020-04-28 00:00:00

  • Heparin-binding epidermal growth factor-like growth factor, a v-Jun target gene, induces oncogenic transformation.

    abstract::Jun is a transcription factor belonging to the activator protein 1 family. A mutated version of Jun (v-Jun) transduced by the avian retrovirus ASV17 induces oncogenic transformation in avian cell cultures and sarcomas in young galliform birds. The oncogenicity of Jun probably results from transcriptional deregulation ...

    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.96.10.5716

    authors: Fu Sl,Bottoli I,Goller M,Vogt PK

    更新日期:1999-05-11 00:00:00

  • Preparation and characterization of a pentaammineruthenium(III) derivative of horse heart ferricytochrome c.

    abstract::A stable complex between pentaammineruthenium(III) and histidine-33 in horse heart ferricytochrome c is formed in the reaction between aquopentaammineruthenium(II) and the protein at pH 7. HPLC of the tryptic hydrolysate of the modified protein was employed to identify the pentaammineruthenium binding site. Spectrosco...

    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.79.22.7052

    authors: Yocom KM,Shelton JB,Shelton JR,Schroeder WA,Worosila G,Isied SS,Bordignon E,Gray HB

    更新日期:1982-11-01 00:00:00

  • Probing large viscosities in glass-formers with nonequilibrium simulations.

    abstract::For decades, scientists have debated whether supercooled liquids stop flowing below a glass transition temperature [Formula: see text] or whether motion continues to slow gradually down to zero temperature. Answering this question is challenging because human time scales set a limit on the largest measurable viscosity...

    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.1705978114

    authors: Jadhao V,Robbins MO

    更新日期:2017-07-25 00:00:00

  • Object grouping based on real-world regularities facilitates perception by reducing competitive interactions in visual cortex.

    abstract::In virtually every real-life situation humans are confronted with complex and cluttered visual environments that contain a multitude of objects. Because of the limited capacity of the visual system, objects compete for neural representation and cognitive processing resources. Previous work has shown that such attentio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,随机对照试验

    doi:10.1073/pnas.1400559111

    authors: Kaiser D,Stein T,Peelen MV

    更新日期:2014-07-29 00:00:00

  • Tumor-suppressive effect of the retinoic acid receptor beta in human epidermoid lung cancer cells.

    abstract::Retinoic acid receptor beta (RAR beta), which codes for a nuclear receptor for retinoic acid, is localized in a chromosomal region frequently deleted in lung cancer cells. The gene is expressed in normal lung tissue and in the majority of the cell lines derived from lung tumors but not in most of the lines derived fro...

    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.90.3.985

    authors: Houle B,Rochette-Egly C,Bradley WE

    更新日期:1993-02-01 00:00:00

  • Epidermal growth factor stimulates tyrosine phosphorylation in the neonatal mouse: association of a M(r) 55,000 substrate with the receptor.

    abstract::Administration of epidermal growth factor (EGF) to neonatal mice resulted in rapid tyrosine phosphorylation of a number of specific substrates in liver, kidney, lung, bladder, skin, and brain as detected by Western blot analysis of tissue homogenates with anti-phosphotyrosine antibodies. In the liver, three prominent ...

    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.89.18.8477

    authors: Donaldson RW,Cohen S

    更新日期:1992-09-15 00:00:00

  • Rapid landscape transformation in South Island, New Zealand, following initial Polynesian settlement.

    abstract::Humans have altered natural patterns of fire for millennia, but the impact of human-set fires is thought to have been slight in wet closed-canopy forests. In the South Island of New Zealand, Polynesians (Māori), who arrived 700-800 calibrated years (cal y) ago, and then Europeans, who settled ∼150 cal y ago, used fire...

    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.1011801107

    authors: McWethy DB,Whitlock C,Wilmshurst JM,McGlone MS,Fromont M,Li X,Dieffenbacher-Krall A,Hobbs WO,Fritz SC,Cook ER

    更新日期:2010-12-14 00:00:00

  • Early stages in DNA binding and uptake during genetic transformation of pneumococci.

    abstract::Ethylenediaminetetraacetate and other divalent-cation-complexing agents greatly stimulate the cellular binding of DNA molecules to competent pneumococci, while the appearance of genetic transformants and nuclease-resistant DNA binding are completely inhibited. Based on this finding, we developed an experimental system...

    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.71.4.1493

    authors: Seto H,Tomasz A

    更新日期:1974-04-01 00:00:00

  • Apolipoprotein E and Alzheimer disease.

    abstract::Inheritance of specific apolipoprotein E (apoE) alleles determines, in large part, the risk and mean age of onset of late-onset familial and sporadic Alzheimer disease. The mechanism by which the apoE isoforms differentially contribute to disease expression is, however, unknown. Isoform-specific differences have been ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.92.11.4725

    authors: Strittmatter WJ,Roses AD

    更新日期:1995-05-23 00:00:00

  • The autophagic machinery ensures nonlytic transmission of mycobacteria.

    abstract::In contrast to mechanisms mediating uptake of intracellular bacterial pathogens, bacterial egress and cell-to-cell transmission are poorly understood. Previously, we showed that the transmission of pathogenic mycobacteria between phagocytic cells also depends on nonlytic ejection through an F-actin based structure, ca...

    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.1423318112

    authors: Gerstenmaier L,Pilla R,Herrmann L,Herrmann H,Prado M,Villafano GJ,Kolonko M,Reimer R,Soldati T,King JS,Hagedorn M

    更新日期:2015-02-17 00:00:00

  • Rare somatic cells from human breast tissue exhibit extensive lineage plasticity.

    abstract::We identified cell surface markers associated with repression of p16(INK4a)/cyclin-dependent kinase inhibitor 2A(CDKN2A), a critical determinant in the acquisition of a plastic state. These cell surface markers allowed direct isolation of rare cells from healthy human breast tissue that exhibit extensive lineage plast...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 临床试验,杂志文章

    doi:10.1073/pnas.1218682110

    authors: Roy S,Gascard P,Dumont N,Zhao J,Pan D,Petrie S,Margeta M,Tlsty TD

    更新日期:2013-03-19 00:00:00

  • Transition state and ground state properties of the helix-coil transition in peptides deduced from high-pressure studies.

    abstract::Volume changes associated with protein folding reactions contain valuable information about the folding mechanism and the nature of the transition state. However, meaningful interpretation of such data requires that overall volume changes be deconvoluted into individual contributions from different structural componen...

    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.1317973110

    authors: Neumaier S,Büttner M,Bachmann A,Kiefhaber T

    更新日期:2013-12-24 00:00:00