The progesterone antagonist RU486 acquires agonist activity upon stimulation of cAMP signaling pathways.

Abstract:

:The protein kinase A stimulator cAMP can potentiate the ability of progestins to induce the transactivation function of the human progesterone receptor (hPR). We questioned in the present study whether cAMP could functionally cooperate with the progestin antagonist RU486. In T47D human breast cancer cells, RU486 behaves as a pure antagonist with respect to induction of the progesterone-responsive mouse mammary tumor virus chloramphenicol acetyltransferase (MMTV-CAT) reporter gene. It fails to stimulate MMTV-CAT expression and completely inhibits induction by the synthetic progestin R5020. However, when RU486 is combined with 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP), MMTV-CAT is induced to levels approaching that stimulated by R5020 alone. Also, RU486 in the presence of 8-Br-cAMP is only partially effective in antagonizing R5020 action. The agonist activity exhibited under these conditions appears to be due to RU486 acting through hPR as evidenced by the fact that 8-Br-cAMP alone has no effect on MMTV-CAT, whereas induction by the combination of 8-Br-cAMP and RU486 is dose responsive to RU486 in a saturable manner and can be inhibited by the type I antiprogestin (prevents hPR-DNA binding) ZK98299, which does not exhibit positive functional cooperation with cAMP. Acquisition of agonist activity in the presence of 8-Br-cAMP also extends to the type II antiprogestin (permits hPR-DNA binding) ZK112993. Since RU486 is also a type II antagonist, these results suggest that detection of functional synergism between cAMP and antiprogestins may require binding of the hPR-antagonist complex to DNA. We propose that cross-talk between second messenger and steroid receptor signal transduction pathways may be one mechanism for resistance to steroid antagonists that frequently develops in breast cancer.

authors

Beck CA,Weigel NL,Moyer ML,Nordeen SK,Edwards DP

doi

10.1073/pnas.90.10.4441

subject

Has Abstract

pub_date

1993-05-15 00:00:00

pages

4441-5

issue

10

eissn

0027-8424

issn

1091-6490

journal_volume

90

pub_type

杂志文章
  • Shear-induced reorganization of renal proximal tubule cell actin cytoskeleton and apical junctional complexes.

    abstract::In this study, we demonstrate that fluid shear stress (FSS)-induced actin cytoskeletal reorganization and junctional formation in renal epithelial cells are nearly completely opposite the corresponding changes in vascular endothelial cells (ECs) [Thi MM et al. (2004) Proc Natl Acad Sci USA 101:16483-16488]. Mouse prox...

    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.0804954105

    authors: Duan Y,Gotoh N,Yan Q,Du Z,Weinstein AM,Wang T,Weinbaum S

    更新日期:2008-08-12 00:00:00

  • Tracking an embryonic L1 retrotransposition event.

    abstract::Long interspersed nuclear elements 1 (L1) are active retrotransposons that reside in many species, including humans and rodents. L1 elements produce an RNA intermediate that is reverse transcribed to DNA and inserted in a new genomic location. We have tagged an active human L1 element (L1(RP)) with a gene encoding enh...

    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.0337627100

    authors: Prak ET,Dodson AW,Farkash EA,Kazazian HH Jr

    更新日期:2003-02-18 00:00:00

  • Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination.

    abstract::Ig class-switch recombination (CSR) is directed by the long and repetitive switch regions and requires activation-induced cytidine deaminase (AID). One of the conserved switch-region sequence motifs (AGCT) is a preferred site for AID-mediated DNA-cytosine deamination. By using somatic gene targeting and recombinase-me...

    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.1018726108

    authors: Han L,Masani S,Yu K

    更新日期:2011-07-12 00:00:00

  • Activation of plant quinate:NAD 3-oxidoreductase by Ca and calmodulin.

    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

    authors: Ranjeva R,Refeno G,Boudet AM,Marmé D

    更新日期:1983-09-01 00:00:00

  • Expanded functions for a family of plant intracellular immune receptors beyond specific recognition of pathogen effectors.

    abstract::Plants and animals deploy intracellular immune receptors that perceive specific pathogen effector proteins and microbial products delivered into the host cell. We demonstrate that the ADR1 family of Arabidopsis nucleotide-binding leucine-rich repeat (NB-LRR) receptors regulates accumulation of the defense hormone sali...

    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.1113726108

    authors: Bonardi V,Tang S,Stallmann A,Roberts M,Cherkis K,Dangl JL

    更新日期:2011-09-27 00:00:00

  • Variation in the sensitivity of organismal body temperature to climate change over local and geographic scales.

    abstract::Global climate change is expected to have broad ecological consequences for species and communities. Attempts to forecast these consequences usually assume that changes in air or water temperature will translate into equivalent changes in a species' organismal body temperature. This simple change is unlikely because 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.0510992103

    authors: Gilman SE,Wethey DS,Helmuth B

    更新日期:2006-06-20 00:00:00

  • Lectin activity as a marker for Hodgkin disease cells.

    abstract::Treatment of cultured Hodgkin disease (HD) cells with neuraminidase results in decreased reactivity of monoclonal antibody VIM-D5 with its antigen, the X hapten, a fucosyl-N-acetyllactosamine. The other feature characteristic of HD cells is the expression of high levels of ectosialyltransferase activity. We present ev...

    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.83.10.3451

    authors: Paietta E,Stockert RJ,Morell AG,Diehl V,Wiernik PH

    更新日期:1986-05-01 00:00:00

  • Type II protein arginine methyltransferase 5 (PRMT5) is required for circadian period determination in Arabidopsis thaliana.

    abstract::Posttranslational modification is an important element in circadian clock function from cyanobacteria through plants and mammals. For example, a number of key clock components are phosphorylated and thereby marked for subsequent ubiquitination and degradation. Through forward genetic analysis we demonstrate that prote...

    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.1011987107

    authors: Hong S,Song HR,Lutz K,Kerstetter RA,Michael TP,McClung CR

    更新日期:2010-12-07 00:00:00

  • Mechanism of deoxyadenosine-induced catabolism of adenine ribonucleotides in adenosine deaminase-inhibited human T lymphoblastoid cells.

    abstract::Loss of ATP accompanying accumulation of dATP has recently been reported to occur in the erythrocytes and lymphoblasts of patients with T lymphocytic leukemia during treatment with deoxycoformycin, an inhibitor of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) that causes the accumulation of deoxyadenosine...

    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.79.8.2673

    authors: Bagnara AS,Hershfield MS

    更新日期:1982-04-01 00:00:00

  • Co-clustering of denatured hemoglobin with band 3: its role in binding of autoantibodies against band 3 to abnormal and aged erythrocytes.

    abstract::Precipitates of hemoglobin, termed Heinz bodies, occur in a fraction of erythrocytes after removal of the spleen and are also observed in aged erythrocytes. This implies that precipitates of hemoglobin might play a particular role in senescent cell recognition. By using immunofluorescence microscopy, evidence is prese...

    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.83.16.6137

    authors: Schlüter K,Drenckhahn D

    更新日期:1986-08-01 00:00:00

  • A long-range regulatory element of Hoxc8 identified by using the pClasper vector.

    abstract::Hox genes are located in highly conserved clusters. The significance of this organization is unclear, but one possibility is that regulatory regions for individual genes are dispersed throughout the cluster and shared with other Hox genes. This hypothesis is supported by studies on several Hox genes in which even larg...

    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.93.6.2426

    authors: Bradshaw MS,Shashikant CS,Belting HG,Bollekens JA,Ruddle FH

    更新日期:1996-03-19 00:00:00

  • Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism.

    abstract::Misalignment between internal circadian rhythmicity and externally imposed behavioral schedules, such as occurs in shift workers, has been implicated in elevated risk of metabolic disorders. To determine underlying mechanisms, it is essential to assess whether and how peripheral clocks are disturbed during shift work ...

    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.1801183115

    authors: Skene DJ,Skornyakov E,Chowdhury NR,Gajula RP,Middleton B,Satterfield BC,Porter KI,Van Dongen HPA,Gaddameedhi S

    更新日期:2018-07-24 00:00:00

  • An experimental system for analyzing response to a morphogen gradient.

    abstract::A recently described experimental system for analyzing the mode of action of a morphogen gradient involves the in situ hybridization of sectioned tissue constructs. In these constructs, a source of activin signaling induces the transcription of several mesodermal genes in blastula animal caps, according to the positio...

    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.93.18.9334

    authors: Gurdon JB,Mitchell A,Ryan K

    更新日期:1996-09-03 00:00:00

  • Cross-polarization/magic-angle sample-spinning C NMR spectroscopic study of chlorophyll a in the solid state.

    abstract::Solid-state cross-polarization/magic-angle sample-spinning (13)C NMR spectra have been recorded on chlorophyll a-water aggregates, methyl pyrochlorophyllide a, and methyl pyropheophorbide a (derivatives that lack a phytyl chain). Spectra have also been collected under a decoupling regime in which resonances of certain...

    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.81.2.641

    authors: Brown CE,Spencer RB,Burger VT,Katz JJ

    更新日期:1984-01-01 00:00:00

  • Ancient DNA reveals the Arctic origin of Viking Age cod from Haithabu, Germany.

    abstract::Knowledge of the range and chronology of historic trade and long-distance transport of natural resources is essential for determining the impacts of past human activities on marine environments. However, the specific biological sources of imported fauna are often difficult to identify, in particular if species have a ...

    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.1710186114

    authors: Star B,Boessenkool S,Gondek AT,Nikulina EA,Hufthammer AK,Pampoulie C,Knutsen H,André C,Nistelberger HM,Dierking J,Petereit C,Heinrich D,Jakobsen KS,Stenseth NC,Jentoft S,Barrett JH

    更新日期:2017-08-22 00:00:00

  • Minor spliceosome components are predominantly localized in the nucleus.

    abstract::Recently, it has been reported that there is a differential subcellular distribution of components of the minor U12-dependent and major U2-dependent spliceosome, and further that the minor spliceosome functions in the cytoplasm. To study the subcellular localization of the snRNA components of both the major and minor ...

    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.0803646105

    authors: Pessa HK,Will CL,Meng X,Schneider C,Watkins NJ,Perälä N,Nymark M,Turunen JJ,Lührmann R,Frilander MJ

    更新日期:2008-06-24 00:00:00

  • Contraction of neuronal branching volume: an anatomic correlate of Pavlovian conditioning.

    abstract::Associative memory of the mollusc Hermissenda crassicornis, previously correlated with changes of specific K+ currents, protein phosphorylation, and increased synthesis of mRNA and specific proteins, is here shown to be accompanied by macroscopic alteration in the structure of a single identified neuron, the medial ty...

    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.87.4.1611

    authors: Alkon DL,Ikeno H,Dworkin J,McPhie DL,Olds JL,Lederhendler I,Matzel L,Schreurs BG,Kuzirian A,Collin C

    更新日期:1990-02-01 00:00:00

  • Painting of fourth, a chromosome-specific protein in Drosophila.

    abstract::Chromosome-specific gene regulation is known thus far only as a mechanism to equalize the transcriptional activity of the single male X chromosome with that of the two female X chromosomes. In Drosophila melanogaster, a complex including the five Male-Specific Lethal (MSL) proteins, "paints" the male X chromosome, med...

    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.111581298

    authors: Larsson J,Chen JD,Rasheva V,Rasmuson-Lestander A,Pirrotta V

    更新日期:2001-05-22 00:00:00

  • SNX-1 and RME-8 oppose the assembly of HGRS-1/ESCRT-0 degradative microdomains on endosomes.

    abstract::After endocytosis, transmembrane cargo reaches endosomes, where it encounters complexes dedicated to opposing functions: recycling and degradation. Microdomains containing endosomal sorting complexes required for transport (ESCRT)-0 component Hrs [hepatocyte growth factor-regulated tyrosine kinase substrate (HGRS-1) 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.1612730114

    authors: Norris A,Tammineni P,Wang S,Gerdes J,Murr A,Kwan KY,Cai Q,Grant BD

    更新日期:2017-01-17 00:00:00

  • An evolving autoimmune microenvironment regulates the quality of effector T cell restimulation and function.

    abstract::Defining the processes of autoimmune attack of tissues is important for inhibiting continued tissue destruction. In type 1 diabetes, it is not known how cytotoxic effector T cell responses evolve over time in the pancreatic islets targeted for destruction. We used two-photon microscopy of live, intact, individual isle...

    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.1322193111

    authors: Friedman RS,Lindsay RS,Lilly JK,Nguyen V,Sorensen CM,Jacobelli J,Krummel MF

    更新日期:2014-06-24 00:00:00

  • Proteomic analysis of skeletal organic matrix from the stony coral Stylophora pistillata.

    abstract::It has long been recognized that a suite of proteins exists in coral skeletons that is critical for the oriented precipitation of calcium carbonate crystals, yet these proteins remain poorly characterized. Using liquid chromatography-tandem mass spectrometry analysis of proteins extracted from the cell-free skeleton 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.1301419110

    authors: Drake JL,Mass T,Haramaty L,Zelzion E,Bhattacharya D,Falkowski PG

    更新日期:2013-03-05 00:00:00

  • Communicating the deadly consequences of global warming for human heat stress.

    abstract::In December of 2015, the international community pledged to limit global warming to below 2 °C above preindustrial (PI) to prevent dangerous climate change. However, to what extent, and for whom, is danger avoided if this ambitious target is realized? We address these questions by scrutinizing heat stress, because 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.1617526114

    authors: Matthews TK,Wilby RL,Murphy C

    更新日期:2017-04-11 00:00:00

  • Alternative starting materials for industrial processes.

    abstract::In the manufacture of chemical feedstocks and subsequent processing into derivatives and materials, the U.S. chemical industry sets the current standard of excellence for technological competitiveness. This world-class leadership is attributed to the innovation and advancement of chemical engineering process technolog...

    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.89.3.821

    authors: Mitchell JW

    更新日期:1992-02-01 00:00:00

  • A molecular phylogeny of the marine red algae (Rhodophyta) based on the nuclear small-subunit rRNA gene.

    abstract::A phylogeny of marine Rhodophyta has been inferred by a number of methods from nucleotide sequences of nuclear genes encoding small subunit rRNA from 39 species in 15 orders. Sequence divergences are relatively large, especially among bangiophytes and even among congeners in this group. Subclass Bangiophycidae appears...

    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.91.15.7276

    authors: Ragan MA,Bird CJ,Rice EL,Gutell RR,Murphy CA,Singh RK

    更新日期:1994-07-19 00:00:00

  • Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans.

    abstract::Functional imaging of the human brain is an increasingly important technique for clinical and cognitive neuroscience research, with functional MRI (fMRI) of the blood oxygen level-dependent (BOLD) response and electroencephalography or magnetoencephalography (MEG) recordings of neural oscillations being 2 of the most ...

    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.0900728106

    authors: Muthukumaraswamy SD,Edden RA,Jones DK,Swettenham JB,Singh KD

    更新日期:2009-05-19 00:00:00

  • CK2 activates kinesin via induction of a conformational change.

    abstract::Kinesin is the canonical plus-end microtubule motor and has been the focus of intense study since its discovery in 1985. We previously demonstrated a time-dependent inactivation of kinesin in vitro that was fully reversible by the addition of purified casein kinase 2 (CK2) and showed that this inactivation/reactivatio...

    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.1321419111

    authors: Mattson-Hoss MK,Niitani Y,Gordon EA,Jun Y,Bardwell L,Tomishige M,Gross SP

    更新日期:2014-05-13 00:00:00

  • Prevention of viral-chemical co-carcinogenesis in vitro by type-specific anti-viral antibody.

    abstract::Low passage Fischer rat embryo cultures, which are normally very resistant to transformation by 3-methylcholanthrene but are highly susceptible when chronically infected with the Rauscher murine leukemia virus, were completely protected from transformation by methylcholanthrene when treated with neutralizing antibody ...

    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.73.1.152

    authors: Price PJ,Bellew TM,King MP,Freeman AE,Gilden RV,Huebner RJ

    更新日期:1976-01-01 00:00:00

  • Natural and sexual selection in a monogamous historical human population.

    abstract::Whether and how human populations exposed to the agricultural revolution are still affected by Darwinian selection remains controversial among social scientists, biologists, and the general public. Although methods of studying selection in natural populations are well established, our understanding of selection in hum...

    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.1118174109

    authors: Courtiol A,Pettay JE,Jokela M,Rotkirch A,Lummaa V

    更新日期:2012-05-22 00:00:00

  • Inactivation of EWS reduces PGC-1α protein stability and mitochondrial homeostasis.

    abstract::EWS (Ewing sarcoma) encodes an RNA/ssDNA binding protein that is frequently rearranged in a number of different cancers by chromosomal translocations. Physiologically, EWS has diverse and essential roles in various organ development and cellular processes. In this study, we uncovered a new role of EWS in mitochondrial...

    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.1504391112

    authors: Park JH,Kang HJ,Lee YK,Kang H,Kim J,Chung JH,Chang JS,McPherron AC,Lee SB

    更新日期:2015-05-12 00:00:00

  • Identification of a two-component fatty acid kinase responsible for host fatty acid incorporation by Staphylococcus aureus.

    abstract::Extracellular fatty acid incorporation into the phospholipids of Staphylococcus aureus occurs via fatty acid phosphorylation. We show that fatty acid kinase (Fak) is composed of two dissociable protein subunits encoded by separate genes. FakA provides the ATP binding domain and interacts with two distinct FakB protein...

    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.1408797111

    authors: Parsons JB,Broussard TC,Bose JL,Rosch JW,Jackson P,Subramanian C,Rock CO

    更新日期:2014-07-22 00:00:00