Abstract:
:The mammary glands of prepubertal estrogen receptor (ER)beta-- mice are morphologically indistinguishable from those of WT littermates. It appears that, although ERbeta is expressed in the mouse mammary gland, it is not involved in ductal growth of the gland. In this study, we examined the possibility that ERbeta has a role in the differentiated function of the mammary gland. Pregnancy is rare in ERbeta-- mice, but an intensive breeding program produced seven pregnant ERbeta-- mice, of which five did not eat their offspring and continued to successful lactation. Histomorphological comparison of lactating glands revealed that alveoli were larger and there was less secretory epithelium in ERbeta-- than in WT mice. Ultrastructural analysis showed abundant milk droplets and normal apical villi in the luminal epithelial cells, but the extracellular matrix and lamina basalis were reduced, and very frequently the interepithelial cell space was increased. Levels of the adhesion molecules, E-cadherin, connexin 32, occludin, and integrin alpha2 were reduced, and no zona occludens was detectable. In addition, there was widespread expression of the proliferation marker, Ki-67, in luminal epithelial cells in ERbeta-- but not in WT mice. These findings suggest a role for ERbeta in organization and adhesion of epithelial cells and hence for differentiated tissue morphology. We speculate that, because a reduced risk for breast cancer is conferred on women who breast-feed at an early age, ERbeta could contribute to this risk reduction by facilitating terminal differentiation of the mammary gland.
journal_name
Proc Natl Acad Sci U S Aauthors
Förster C,Mäkela S,Wärri A,Kietz S,Becker D,Hultenby K,Warner M,Gustafsson JAdoi
10.1073/pnas.192561299keywords:
subject
Has Abstractpub_date
2002-11-26 00:00:00pages
15578-83issue
24eissn
0027-8424issn
1091-6490pii
192561299journal_volume
99pub_type
杂志文章abstract::We present a model for transposition that allows a choice between cointegrate formation (replicon fusion) and direct transposition. We propose that initiation of the process occurs by invasion of the target DNA by a single-stranded end of the transposable element. This leads to nicking of one of the DNA strands of 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.78.8.4858
更新日期:1981-08-01 00:00:00
abstract::Parts of the primary structure of the NAD-specific glutamate dehydrogenase [L-glutamate:NAD oxidoreductase (deaminating), EC 1.4.1.2] from Neurospora crassa are presented. Segments of the sequence representing 886 unique amino-acid residues have been determined; the largest contains 267 residues. There are only short ...
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.72.12.4891
更新日期:1975-12-01 00:00:00
abstract::Goblet-cell hyperplasia is a critical pathological feature in hypersecretory diseases of airways. However, the underlying mechanisms are unknown, and no effective therapy exists. Here we show that stimulation of epidermal growth factor receptors (EGF-R) by its ligands, EGF and transforming growth factor alpha (TGFalph...
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.96.6.3081
更新日期:1999-03-16 00:00:00
abstract::The RIG-G gene, originally isolated from an acute promyelocytic leukemia cell line NB4, codes for a 60-kDa cytoplasmic protein that is induced by all-trans retinoic acid (ATRA) treatment along with the induction of morphological differentiation of NB4 cells. Here, we provide evidence that ectopic expression of Rig-G 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.0607830103
更新日期:2006-10-31 00:00:00
abstract::Alpha-actinin-4 is a widely expressed protein that employs an actin-binding site with two calponin homology domains to crosslink actin filaments (F-actin) in a Ca(2+)-sensitive manner in vitro. An inherited, late-onset form of kidney failure is caused by point mutations in the alpha-actinin-4 actin-binding domain. Her...
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.0702451104
更新日期:2007-10-09 00:00:00
abstract::Emergence of antiestrogen-resistant cells in MCF-7 cells during suppression of estrogen signaling is a widely accepted model of acquired breast cancer resistance to endocrine therapy. To obtain insight into the genomic basis of endocrine therapy resistance, we characterized MCF-7 monoclonal sublines that survived 21-d...
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.0907560106
更新日期:2009-08-25 00:00:00
abstract::Damage to the protooncogene MYC has been implicated in the genesis of diverse human tumors, but the tumorigenic potential of the isolated gene has been disputed. Here we report the use of a retroviral vector to test the potency of human MYC for neoplastic transformation in avian cells. We found that sustained and abun...
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.87.6.2102
更新日期:1990-03-01 00:00:00
abstract::The unique specificity of monoclonal antibodies (Ab) was combined with the cell-killing function of the cytolytic alternative pathway of complement. The functionally C3b-like glycoprotein of cobra venom was linked to a murine monoclonal Ab directed to a human melanoma-associated antigen by a disulfide bond, by using 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.78.12.7707
更新日期:1981-12-01 00:00:00
abstract::Marked hypoalphalipoproteinemia was found together with relatively low serum cholesterol, triacylglycerol, and LDL levels in a triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1)-deficient Hungarian family, especially in the two compound-heterozygote brothers. Apart from a slight...
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.92.1.268
更新日期:1995-01-03 00:00:00
abstract::It has been found that the mutator phenotype of the recA441 and recA730 strains that express the SOS response constitutively is suppressed by pIP1, a high-copy plasmid carrying the dnaQ gene encoding the 3'----5' exonuclease subunit (epsilon) of DNA polymerase III. We have constructed plasmid pIP11, in which the dnaQ ...
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.85.23.9124
更新日期:1988-12-01 00:00:00
abstract::Apoptotic cells contain nuclear autoantigens that may initiate a systemic autoimmune response. To explore the mechanism of antibody binding to apoptotic cells, 3H9, a murine autoantibody with dual specificity for phospholipids and DNA, was used. H chain mutants of 3H9 were constructed, expressed as single-chain Fv (sc...
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.241510698
更新日期:2001-11-20 00:00:00
abstract::Molecular diversity of ion channel structure and function underlies variability in electrical signaling in nerve, muscle, and nonexcitable cells. Regulation by variable auxiliary subunits is a major mechanism to generate tissue- or cell-specific diversity of ion channel function. Mammalian large-conductance, voltage- ...
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.1205435109
更新日期:2012-05-15 00:00:00
abstract::Stabilization of neuronal activity by homeostatic control systems is fundamental for proper functioning of neural circuits. Failure in neuronal homeostasis has been hypothesized to underlie common pathophysiological mechanisms in a variety of brain disorders. However, the key molecules regulating homeostasis in centra...
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.1424810112
更新日期:2015-06-23 00:00:00
abstract::Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of prima...
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.1404167111
更新日期:2015-01-13 00:00:00
abstract::X-ray structures of bovine heart cytochrome c oxidase have suggested that the enzyme, which reduces O(2) in a process coupled with a proton pumping process, contains a proton pumping pathway (H-pathway) composed of a hydrogen bond network and a water channel located in tandem across the enzyme. The hydrogen bond netwo...
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.0611627104
更新日期:2007-03-06 00:00:00
abstract::A change in the conformation of the active site of scallop myosin under the influence of regulatory amounts of Ca2+ has been identified by use of the ADP photoaffinity analog 2-[(4-azido-2-nitrophenyl)amino]ethyl diphosphate (NANDP). NANDP, trapped at the active site with Mn2+ and vanadate, photolabeled preferentially...
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.90.1.35
更新日期:1993-01-01 00:00:00
abstract::Control of transcription and enzyme activities are two interwoven regulatory systems essential for the function of a metabolic node. Saccharomyces cerevisiae strains differing in enzyme activities at the chorismate branch point of aromatic amino acid biosynthesis were constructed by recombinant DNA technology. Express...
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.240469697
更新日期:2000-12-05 00:00:00
abstract::An intermolecular intercalation of base pairs was found at the CA step in the I222 crystal structure of the RNA.DNA hybrid, r(CAAAGAAAAG).d(CTTTTCTTTG), which contains two-thirds of the polypurine tract sequence of HIV-1 with a substitution of cytosine for the initial adenine. This sequence crystallized in both P21212...
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.1533326100
更新日期:2003-08-05 00:00:00
abstract::Proteomics were used to identify the proteins from the eukaryotic unicellular green alga Chlamydomonas reinhardtii that can be reduced by thioredoxin. These proteins were retained specifically on a thioredoxin affinity column made of a monocysteinic thioredoxin mutant able to form mixed disulfides with its targets. 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.0402221101
更新日期:2004-05-11 00:00:00
abstract::Although potassium channels play a variety of roles in shaping the electrical properties of neurons, little is known about how these channels are constituted in neurons. To examine the assembly and physiological function of A-type K+ channels in mature differentiated neurons, we have developed a highly efficient gene ...
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.89.3.1133
更新日期:1992-02-01 00:00:00
abstract::Human gene MAGE-1 encodes tumor-specific antigens that are recognized on melanoma cells by autologous cytolytic T lymphocytes. This gene is expressed in a significant proportion of tumors of various histological types, but not in normal tissues except male germ-line cells. We reported previously that reporter genes dr...
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.93.14.7149
更新日期:1996-07-09 00:00:00
abstract::In an 1885 paper, E. Picard defined a subgroup Tau(Lambda) of PU(2,1) generated by monodromies and depending on parameters Lambda = (lambda(1),lambda(2),lambda(3),lambda(4)), 0 < lambda(i) < 1, < lambda(i) < 3, lambda(i) + lambda(j) >/= 1, 1 = i < j = 4. The family Tau(Lambda) resembles the family of groups Tau([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.78.10.5948
更新日期:1981-10-01 00:00:00
abstract::In eukaryotic cells the concentration of dNTP is highest in S phase and lowest in G1 phase and is controlled by ribonucleotide reductase (RNR). RNR activity is eliminated in all eukaryotes in G1 phase by a variety of mechanisms: transcriptional regulation, small inhibitory proteins, and protein degradation. After acti...
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.0610585104
更新日期:2007-01-23 00:00:00
abstract::Thioredoxins are 12-kDa proteins functional in the regulation of cellular processes throughout the animal, plant, and microbial kingdoms. Growing evidence with seeds suggests that an h-type of thioredoxin, reduced by NADPH via NADP-thioredoxin reductase, reduces disulfide bonds of target proteins and thereby acts as 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.071041998
更新日期:2001-04-10 00:00:00
abstract::Alzheimer beta/A4 amyloid precursor protein (APP) has been suggested to play a central role in the pathogenesis of Alzheimer disease. We have measured the content of different species of APP holoprotein and carboxyl-terminal fragments in human brains from young individuals, nondemented aged individuals, and aged indiv...
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.88.20.8910
更新日期:1991-10-15 00:00:00
abstract::Hypertension, a remediable risk factor for stroke, cardiovascular disease, and renal failure, affects 50 million individuals in the United States alone. African Americans (blacks) have a higher incidence and prevalence of hypertension and hypertension-associated target organ damage compared with Caucasian Americans (w...
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.050420897
更新日期:2000-03-28 00:00:00
abstract::Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves...
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.1819246116
更新日期:2019-04-02 00:00:00
abstract::The design principles of spider dragline silk, nature's high-performance fiber, are still largely unknown, in particular for the noncrystalline glycine-rich domains, which form the bulk of the material. Here we apply two-dimensional solid-state NMR to determine the distribution of the backbone torsion angles (phi,psi)...
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.152162299
更新日期:2002-08-06 00:00:00
abstract::Granulocyte-colony stimulating factor (G-CSF) induces differentiation of M1 murine myeloid leukemia cells into mature granulocytes/macrophages and also causes accumulation of the cells in the G1 phase of the cell cycle. We examined, therefore, whether synchronization of M1 cells in the G1 phase could affect G-CSF-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.83.12.4317
更新日期:1986-06-01 00:00:00
abstract::The neuraminidase inhibitors oseltamivir and zanamivi are used to treat H5N1 influenza. However, oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. Moreover, reassortment between H5N1 viruses and oseltamvir-resistant human H1N1 viruses currently circulating could create oseltamivi...
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.0909603107
更新日期:2010-01-12 00:00:00