The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1.

Abstract:

:Homeobox genes constitute a large family of transcription factors that are essential during normal development and are often dysregulated in cancer. However, the molecular mechanisms by which homeobox genes influence cancer remain largely unknown. Here we show that the tissue-restricted cyclin A1 is a transcriptional target of the Six1 homeoprotein. Both genes are expressed in the embryonic but not the terminally differentiated mammary gland, and Six1-knockout mice show a dramatic reduction of cyclin A1 in the embryonic mammary gland. In addition, both genes are reexpressed in breast cancers. Six1 overexpression increases cyclin A1 mRNA levels and activity, cell proliferation, and tumor volume, whereas Six1 down-regulation decreases cyclin A1 mRNA levels and proliferation. Overexpression of Six1 in wild-type mouse embryonic fibroblasts, but not in knockout variants lacking the cyclin A1 gene, induces cell proliferation. Furthermore, inhibition of cyclin A1 in Six1-overexpressing mammary carcinoma cells decreases proliferation. Together these results demonstrate that cyclin A1 is required for the proliferative effect of Six1. We conclude that Six1 overexpression reinstates an embryonic pathway of proliferation in breast cancer by up-regulating cyclin A1.

authors

Coletta RD,Christensen K,Reichenberger KJ,Lamb J,Micomonaco D,Huang L,Wolf DM,Müller-Tidow C,Golub TR,Kawakami K,Ford HL

doi

10.1073/pnas.0401139101

keywords:

subject

Has Abstract

pub_date

2004-04-27 00:00:00

pages

6478-83

issue

17

eissn

0027-8424

issn

1091-6490

pii

0401139101

journal_volume

101

pub_type

杂志文章
  • Holdase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity in Drosophila.

    abstract::Alzheimer's disease (AD) is the most prevalent of a large group of related proteinopathies for which there is currently no cure. Here, we used Drosophila to explore a strategy to block Aβ42 neurotoxicity through engineering of the Heat shock protein 70 (Hsp70), a chaperone that has demonstrated neuroprotective activit...

    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.1608045113

    authors: Fernandez-Funez P,Sanchez-Garcia J,de Mena L,Zhang Y,Levites Y,Khare S,Golde TE,Rincon-Limas DE

    更新日期:2016-08-30 00:00:00

  • On the mechanism of chaperone activity of the small heat-shock protein of Methanococcus jannaschii.

    abstract::The small heat-shock protein (sHSP) from Methanococcus jannaschii (Mj HSP16.5) forms a homomeric complex of 24 subunits and has an overall structure of a multiwindowed hollow sphere with an external diameter of approximately 120 A and an internal diameter of approximately 65 A with six square "windows" of approximatel...

    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.1032940100

    authors: Kim R,Lai L,Lee HH,Cheong GW,Kim KK,Wu Z,Yokota H,Marqusee S,Kim SH

    更新日期:2003-07-08 00:00:00

  • Isolation and characterization of a cDNA encoding Drosophila transcription factor TFIIB.

    abstract::A Drosophila cDNA encoding a human transcription factor TFIIB homologue was isolated by PCR methods. The deduced amino acid sequence indicates 85% sequence similarity with human TFIIB, and the corresponding cDNA product expressed in Escherichia coli is interchangeable with human TFIIB for both basal and GAL4-VP16-indu...

    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.89.7.2839

    authors: Yamashita S,Wada K,Horikoshi M,Gong DW,Kokubo T,Hisatake K,Yokotani N,Malik S,Roeder RG,Nakatani Y

    更新日期:1992-04-01 00:00:00

  • Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation.

    abstract::The forebrain cholinergic system promotes higher brain function in part by signaling through the M(1) muscarinic acetylcholine receptor (mAChR). During Alzheimer's disease (AD), these cholinergic neurons degenerate, therefore selectively activating M(1) receptors could improve cognitive function in these patients whil...

    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.0900903106

    authors: Ma L,Seager MA,Wittmann M,Jacobson M,Bickel D,Burno M,Jones K,Graufelds VK,Xu G,Pearson M,McCampbell A,Gaspar R,Shughrue P,Danziger A,Regan C,Flick R,Pascarella D,Garson S,Doran S,Kreatsoulas C,Veng L,Lindsley C

    更新日期:2009-09-15 00:00:00

  • TNF-alpha from inflammatory dendritic cells (DCs) regulates lung IL-17A/IL-5 levels and neutrophilia versus eosinophilia during persistent fungal infection.

    abstract::Aspergillus fumigatus is commonly associated with allergic bronchopulmonary aspergillosis in patients with severe asthma in which chronic airway neutrophilia predicts a poor outcome. We were able to recapitulate fungus-induced neutrophilic airway inflammation in a mouse model in our efforts to understand the underlyin...

    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.1015476108

    authors: Fei M,Bhatia S,Oriss TB,Yarlagadda M,Khare A,Akira S,Saijo S,Iwakura Y,Fallert Junecko BA,Reinhart TA,Foreman O,Ray P,Kolls J,Ray A

    更新日期:2011-03-29 00:00:00

  • The players in a mutualistic symbiosis: insects, bacteria, viruses, and virulence genes.

    abstract::Aphids maintain mutualistic symbioses involving consortia of coinherited organisms. All possess a primary endosymbiont, Buchnera, which compensates for dietary deficiencies; many also contain secondary symbionts, such as Hamiltonella defensa, which confers defense against natural enemies. Genome sequences of uncultiva...

    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.0507029102

    authors: Moran NA,Degnan PH,Santos SR,Dunbar HE,Ochman H

    更新日期:2005-11-22 00:00:00

  • Nuclear magnetic resonance imaging and spectroscopy of human brain function.

    abstract::The techniques of in vivo magnetic resonance (MR) imaging and spectroscopy have been established over the past two decades. Recent applications of these methods to study human brain function have become a rapidly growing area of research. The development of methods using standard MR contrast agents within the cerebral...

    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.90.8.3127

    authors: Shulman RG,Blamire AM,Rothman DL,McCarthy G

    更新日期:1993-04-15 00:00:00

  • Complex oncogene dependence in microRNA-125a-induced myeloproliferative neoplasms.

    abstract::Deregulation of microRNA (miRNA) expression can lead to cancer initiation and progression. However, limited information exists on the function of miRNAs in cancer maintenance. We examined these issues in the case of myeloproliferative diseases and neoplasms (MPN), a collection of hematopoietic neoplasms regarded as 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.1213196109

    authors: Guo S,Bai H,Megyola CM,Halene S,Krause DS,Scadden DT,Lu J

    更新日期:2012-10-09 00:00:00

  • COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex.

    abstract::Postnatal development and adult function of the central nervous system are dependent on the capacity of neurons to effect long-term changes of specific properties in response to neural activity. This neuronal response has been demonstrated to be tightly correlated with the expression of a set of regulatory genes which...

    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.93.6.2317

    authors: Kaufmann WE,Worley PF,Pegg J,Bremer M,Isakson P

    更新日期:1996-03-19 00:00:00

  • Substrate selectivity in arginine-dependent acid resistance in enteric bacteria.

    abstract::To successfully colonize the human gut, enteric bacteria must activate acid resistance systems to survive the extreme acidity (pH 1.5-3.5) of the stomach. The antiporter AdiC is the master orchestrator of the arginine-dependent system. Upon acid shock, it imports extracellular arginine (Arg) into the cytoplasm, provid...

    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.1301442110

    authors: Tsai MF,Miller C

    更新日期:2013-04-09 00:00:00

  • Developmental regulation of glutamine synthetase and carbonic anhydrase II in neural retina.

    abstract::Glutamine synthetase (GS) is expressed in the neural retina only in Muller glia cells and is inducible with cortisol. A chicken genomic clone that contains at least part of the coding region for the GS enzyme was used to investigate developmental changes in the level of GS mRNA in embryonic chicken retina. A major GS ...

    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.83.23.9060

    authors: Vardimon L,Fox LE,Moscona AA

    更新日期:1986-12-01 00:00:00

  • Crystal structure of the bacteriophage T4 late-transcription coactivator gp33 with the β-subunit flap domain of Escherichia coli RNA polymerase.

    abstract::Activated transcription of the bacteriophage T4 late genes, which is coupled to concurrent DNA replication, is accomplished by an initiation complex containing the host RNA polymerase associated with two phage-encoded proteins, gp55 (the basal promoter specificity factor) and gp33 (the coactivator), as well as the DNA...

    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.1113328108

    authors: Twist KA,Campbell EA,Deighan P,Nechaev S,Jain V,Geiduschek EP,Hochschild A,Darst SA

    更新日期:2011-12-13 00:00:00

  • Control of excision frequency of maize transposable element Ds in Petunia protoplasts.

    abstract::The complete coding region of maize transposable element Ac and truncated but active derivatives of it were placed under the control of promoters of different strength and tested for the ability to excise transposable element Ds from a beta-glucuronidase reporter gene in a cotransfection assay in Petunia protoplasts. ...

    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.89.12.5552

    authors: Becker D,Lütticke R,Li M,Starlinger P

    更新日期:1992-06-15 00:00:00

  • Composition-based prediction and rational manipulation of prion-like domain recruitment to stress granules.

    abstract::Mutations in a number of stress granule-associated proteins have been linked to various neurodegenerative diseases. Several of these mutations are found in aggregation-prone prion-like domains (PrLDs) within these proteins. In this work, we examine the sequence features governing PrLD localization to stress granules u...

    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.1912723117

    authors: Boncella AE,Shattuck JE,Cascarina SM,Paul KR,Baer MH,Fomicheva A,Lamb AK,Ross ED

    更新日期:2020-03-17 00:00:00

  • Temperature-sensitive mutations in Drosophila melanogaster. V. A mutation affecting concentrations of pteridines.

    abstract::A temperature-sensitive ras allele has an effective lethal phase at 29 degrees C about 12 hr after pupation and a temperature-sensitive period for lethality beginning midway through the third larval instar and ending around pupation. The mutation also alters the quantity of pteridines present in the eyes, testes, and ...

    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.67.3.1101

    authors: Grigliatti T,Suzuki DT

    更新日期:1970-11-01 00:00:00

  • Laccase detoxification mediates the nutritional alliance between leaf-cutting ants and fungus-garden symbionts.

    abstract::Leaf-cutting ants combine large-scale herbivory with fungus farming to sustain advanced societies. Their stratified colonies are major evolutionary achievements and serious agricultural pests, but the crucial adaptations that allowed this mutualism to become the prime herbivorous component of neotropical ecosystems ha...

    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.1212709110

    authors: De Fine Licht HH,Schiøtt M,Rogowska-Wrzesinska A,Nygaard S,Roepstorff P,Boomsma JJ

    更新日期:2013-01-08 00:00:00

  • Anisotropy of cell adhesive microenvironment governs cell internal organization and orientation of polarity.

    abstract::Control of the establishment of cell polarity is an essential function in tissue morphogenesis and renewal that depends on spatial cues provided by the extracellular environment. The molecular role of cell-cell or cell-extracellular matrix (ECM) contacts on the establishment of cell polarity has been well characterize...

    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.0609267103

    authors: Théry M,Racine V,Piel M,Pépin A,Dimitrov A,Chen Y,Sibarita JB,Bornens M

    更新日期:2006-12-26 00:00:00

  • Loss of insulin response to glucose but not arginine during the development of autoimmune diabetes in BB/W rats: relationships to islet volume and glucose transport rate.

    abstract::The insulin and glucagon responses to 10 mM glucose and 10 mM arginine were studied in pancreata isolated from nondiabetic diabetes-prone and diabetes-resistant BB/W rats at 60, 80, and 140 days of age and in diabetic BB/W rats on the 1st and 14th days of their diabetes. In the former group the insulin response to glu...

    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.83.24.9749

    authors: Tominaga M,Komiya I,Johnson JH,Inman L,Alam T,Moltz J,Crider B,Stefan Y,Baetens D,McCorkle K

    更新日期:1986-12-01 00:00:00

  • Dynamic regulation of functionally distinct virus-specific T cells.

    abstract::The functional capacities of CD8(+) T cells important for virus clearance are influenced by interactions with antigen presenting cells (APCs) and CD4(+) T cells during initial selection, subsequent expansion, and development of memory. Recently, investigators have shown that polyfunctional T cells correlate best with ...

    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.0915168107

    authors: Ndhlovu ZM,Oelke M,Schneck JP,Griffin DE

    更新日期:2010-02-23 00:00:00

  • Amorphous layer around aragonite platelets in nacre.

    abstract::We reveal that the aragonite CaCO3 platelets in nacre of Haliotis laevigata are covered with a continuous layer of disordered amorphous CaCO3 and that there is no protein interaction with this layer. This finding contradicts classical paradigms of biomineralization, e.g., an epitaxial match between the structural orga...

    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.0502577102

    authors: Nassif N,Pinna N,Gehrke N,Antonietti M,Jäger C,Cölfen H

    更新日期:2005-09-06 00:00:00

  • Modification of EWS/WT1 functional properties by phosphorylation.

    abstract::In many human cancers, tumor-specific chromosomal rearrangements are known to create chimeric products with the ability to transform cells. The EWS/WT1 protein is such a fusion product, resulting from a t(11;22) chromosomal translocation in desmoplastic small round cell tumors, where 265 aa from the EWS amino terminus...

    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.96.25.14300

    authors: Kim J,Lee JM,Branton PE,Pelletier J

    更新日期:1999-12-07 00:00:00

  • Improved protein structure prediction using predicted interresidue orientations.

    abstract::The prediction of interresidue contacts and distances from coevolutionary data using deep learning has considerably advanced protein structure prediction. Here, we build on these advances by developing a deep residual network for predicting interresidue orientations, in addition to distances, and a Rosetta-constrained...

    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.1914677117

    authors: Yang J,Anishchenko I,Park H,Peng Z,Ovchinnikov S,Baker D

    更新日期:2020-01-21 00:00:00

  • Messenger RNA for hepatic tryptophan oxygenase: its partial purification, its translation in a heterologous cell-free system, and its control by glucocorticoid hormones.

    abstract::Messenger RNA from rat liver was partially purified by chromatography on cellulose on the basis of its poly(A) content. Microgram amounts of this RNA stimulate protein synthesis manyfold in a heterologous cell-free system, derived from Krebs ascites cells supplemented with reticulocyte initiation factors. The messenge...

    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.70.4.1218

    authors: Schutz G,Beato M,Feigelson P

    更新日期:1973-04-01 00:00:00

  • Replication initiator protein of plasmid R6K autoregulates its own synthesis at the transcriptional step.

    abstract::The replication initiator protein of plasmid R6K preferentially repressed transcription initiated in vitro from the promoter of the initiator protein cistron. DNase I protection experiments revealed that the sequences in the region of the promoter recognized by the initiator protein partially overlapped the sequences ...

    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.82.9.2574

    authors: Kelley W,Bastia D

    更新日期:1985-05-01 00:00:00

  • Nerve growth factor: activation of the classical complement pathway by specific substitution for component C1-.

    abstract::The interaction of homogeneous preparations of mouse submandibular gland nerve growth factor (NGF) with the classical complement pathway was studied. NGF was found to be capable of carrying out the enzyme activities of the first component (C1-) of the classical complement pathway (i.e., the cleavage of zymogen C4 and ...

    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.79.8.2519

    authors: Boyle MD,Young M

    更新日期:1982-04-01 00:00:00

  • Direct observation of hole transfer through double-helical DNA over 100 A.

    abstract::Mechanism of photo-induced electron transfer and the subsequent hole transfer in DNA has been studied extensively, but so far we are not aware of any reliable report of the observation of the long-distance hole-transfer process. In this article, we demonstrate the results of direct observation for the long-distance ho...

    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.0402756101

    authors: Takada T,Kawai K,Fujitsuka M,Majima T

    更新日期:2004-09-28 00:00:00

  • Locus on human X chromosome for dihydrotestosterone receptor and androgen insensitivity.

    abstract::We have studied androgen binding characteristics of cells for androgen insensitivity from an obligate heterozygote, who is the mother of three male pseudohermaphrodites with dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) receptor deficiency. Specific dihydrotestosterone binding by skin fibroblasts from he...

    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.72.4.1469

    authors: Meyer WJ 3rd,Migeon BR,Migeon CJ

    更新日期:1975-04-01 00:00:00

  • pH-dependent transition between delocalized and trapped valence states of a CuA center and its possible role in proton-coupled electron transfer.

    abstract::A pH-dependent transition between delocalized and trapped mixed valence states of an engineered CuA center in azurin has been investigated by UV-visible absorption and electron paramagnetic resonance spectroscopic techniques. At pH 7.0, the CuA azurin displays a typical delocalized mixed valence dinuclear [Cu(1.5).......

    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.0403473101

    authors: Hwang HJ,Lu Y

    更新日期:2004-08-31 00:00:00

  • Synthesis and secretion of proteins resembling platelet-derived growth factor by human glioblastoma and fibrosarcoma cells in culture.

    abstract::Immunoprecipitation of proteins extracted from metabolically labeled human glioblastoma and fibrosarcoma cells with antiserum to platelet-derived growth factor (PDGF) showed that these cells express and secrete proteins that are recognized specifically by the antiserum. The molecular masses of immunoprecipitated 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.82.8.2404

    authors: Pantazis P,Pelicci PG,Dalla-Favera R,Antoniades HN

    更新日期:1985-04-01 00:00:00

  • Control of bud activation by an auxin transport switch.

    abstract::In many plant species only a small proportion of buds yield branches. Both the timing and extent of bud activation are tightly regulated to produce specific branching architectures. For example, the primary shoot apex can inhibit the activation of lateral buds. This process is termed apical dominance and is dependent ...

    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.0906696106

    authors: Prusinkiewicz P,Crawford S,Smith RS,Ljung K,Bennett T,Ongaro V,Leyser O

    更新日期:2009-10-13 00:00:00