Abstract:
:To determine if Neu is dominant over transforming growth factor beta (TGF-beta), we crossed mouse mammary tumor virus (MMTV)-Neu mice with MMTV-TGF-beta1(S223/225) mice expressing active TGF-beta1 in the mammary gland. Bigenic (NT) and Neu-induced mammary tumors developed with a similar latency. The bigenic tumors and their metastases were less proliferative than those occurring in MMTV-Neu mice. However, NT tumors exhibited less apoptosis and were more locally invasive and of higher histological grade. NT mice exhibited more circulating tumor cells and lung metastases than Neu mice, while NT tumors contained higher levels of phosphorylated (active) Smad2, Akt, mitogen-activated protein kinase (MAPK), and p38, as well as vimentin content and Rac1 activity in situ than tumors expressing Neu alone. Ex vivo, NT cells exhibited higher levels of P-Akt and P-MAPK than Neu cells. These were inhibited by the TGF-beta inhibitor-soluble TGF-beta type II receptor (TbetaRII:Fc), suggesting they were activated by autocrine TGF-beta. TGF-beta stimulated migration of Neu cells into surrounding matrix, while the soluble TGF-beta inhibitor abrogated motility and invasiveness of NT cells. These data suggest that (i) the antimitogenic and prometastatic effects of TGF-beta can exist simultaneously and (ii) Neu does not abrogate TGF-beta-mediated antiproliferative action but can synergize with TGF-beta in accelerating metastatic tumor progression.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Muraoka RS,Koh Y,Roebuck LR,Sanders ME,Brantley-Sieders D,Gorska AE,Moses HL,Arteaga CLdoi
10.1128/mcb.23.23.8691-8703.2003subject
Has Abstractpub_date
2003-12-01 00:00:00pages
8691-703issue
23eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章abstract::In Drosophila and several other metazoan organisms, there are two genes that encode related but distinct homologs of ADA2-type transcriptional adaptors. Here we describe mutations of the two Ada2 genes of Drosophila melanogaster. By using mutant Drosophila lines, which allow the functional study of individual ADA2s, w...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.18.8215-8227.2005
更新日期:2005-09-01 00:00:00
abstract::The c-Myc oncoprotein (Myc) controls cell fate by regulating gene transcription in association with a DNA-binding partner, Max. While Max lacks a transcription regulatory domain, the N terminus of Myc contains a transcription activation domain (TAD) that recruits cofactor complexes containing the histone acetyltransfe...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.23.10220-10234.2005
更新日期:2005-12-01 00:00:00
abstract::To examine the role of clathrin-dependent insulin receptor internalization in insulin-stimulated signal transduction events, we expressed a dominant-interfering mutant of dynamin (K44A/dynamin) by using a recombinant adenovirus in the H4IIE hepatoma and 3T3L1 adipocyte cell lines. Expression of K44A/dynamin inhibited ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.7.3862
更新日期:1998-07-01 00:00:00
abstract::The Fanconi anemia (FA) pathway is a DNA damage-activated signaling pathway which regulates cellular resistance to DNA cross-linking agents. Cloned FA genes and proteins cooperate in this pathway, and monoubiquitination of FANCD2 is a critical downstream event. The cell cycle checkpoint kinase ATR is required for the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02018-05
更新日期:2006-09-01 00:00:00
abstract::The TIS11 primary response gene is rapidly and transiently induced by both 12-O-tetradecanoylphorbol-13-acetate and growth factors. The predicted TIS11 protein contains a 6-amino-acid repeat, YKTELC. We cloned two additional cDNAs, TIS11b and TIS11d, that contain the YKTELC sequence. TIS11, TIS11b, and TIS11d proteins...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.3.1754
更新日期:1991-03-01 00:00:00
abstract::The imprinted expression of the H19 and Igf2 genes in the mouse is controlled by an imprinting control center (ICR) whose activity is regulated by parent-of-origin differences in methylation. The only protein that has been implicated in ICR function is the zinc-finger protein CTCF, which binds at multiple sites within...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.10.3855-3863.2005
更新日期:2005-05-01 00:00:00
abstract::The mammalian ABL1 gene encodes the ubiquitously expressed nonreceptor tyrosine kinase ABL. In response to growth factors, cytokines, cell adhesion, DNA damage, oxidative stress, and other signals, ABL is activated to stimulate cell proliferation or differentiation, survival or death, retraction, or migration. ABL als...
journal_title:Molecular and cellular biology
pub_type: 杂志文章,评审
doi:10.1128/MCB.01454-13
更新日期:2014-04-01 00:00:00
abstract::Chromatin remodeling is central to the regulation of transcription elongation. We demonstrate that the conserved Saccharomyces cerevisiae histone chaperone Nap1 associates with chromatin. We show that Nap1 regulates transcription of PHO5, and the increase in transcript level and the higher phosphatase activity plateau...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02136-07
更新日期:2008-04-01 00:00:00
abstract::Determining the roles of Rel/NF-kappaB transcription factors in mouse skin development with loss-of-function mutants has been limited by redundancy among these proteins and by embryonic lethality associated with the absence of RelA. Using mice lacking RelA and c-rel, which survive throughout embryogenesis on a tumor n...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.13.5733-5745.2004
更新日期:2004-07-01 00:00:00
abstract::Wnt signaling plays an important role in the regulation of bone formation and bone mass. The mechanisms that regulate canonical Wnt signaling in osteoblasts are not fully understood. We show here a novel mechanism by which the adhesion molecule N-cadherin interacts with the Wnt coreceptor LRP5 and regulates canonical ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00349-08
更新日期:2009-02-01 00:00:00
abstract::Ras proteins can activate at least three classes of downstream target proteins: Raf kinases, phosphatidylinositol-3 phosphate (PI3) kinase, and Ral-specific guanine nucleotide exchange factors (Ral-GEFs). In NIH 3T3 cells, activated Ral-GEFs contribute to Ras-induced cell proliferation and oncogenic transformation by ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.3.1731
更新日期:1999-03-01 00:00:00
abstract::Glutamine is the preferred source of nitrogen of Neurospora crassa. In its presence and that of the gene product of MS5 (nmr-1), the fungus represses the assimilation of less preferred forms of nitrogen, such as nitrate. In the absence of glutamine and the presence of the product of gene nit-2, less preferred forms of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.9.4113
更新日期:1989-09-01 00:00:00
abstract::RSC is an essential chromatin remodeling complex in Saccharomyces cerevisiae that performs central roles in transcriptional regulation and cell cycle progression. Here we identify Htl1 as a novel factor that associates with the RSC complex both physically and functionally. We isolated HTL1 through a genetic screen for...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.23.8165-8174.2002
更新日期:2002-12-01 00:00:00
abstract::TRIF is an essential adaptor for Toll-like receptor 3/4 (TLR3/4) signaling to activate transcription factor interferon regulatory factor 3 (IRF-3). We examined the molecular mechanism of TLR3 signaling and found that TLR3 stimulation by double-stranded RNA (dsRNA) induces phosphorylation of TRIF at Ser210 and is requi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00509-19
更新日期:2020-02-12 00:00:00
abstract::To identify novel genes that play critical roles in mediating bone morphogenetic protein (BMP) signal pathways, we performed a yeast two-hybrid screen using Smad1 as bait. A novel mouse Krüppel-type zinc finger protein, mZnf8, was isolated. Interactions between mZnf8 and Smad proteins were further analyzed with variou...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.21.7633-7644.2002
更新日期:2002-11-01 00:00:00
abstract::We investigated various parameters associated with the initial selection of mouse 3T6 cells for resistance to single concentrations of methotrexate and characterized resistant colonies for the presence of additional (amplified) copies of the dihydrofolate reductase gene. Our results indicate that the frequency of occu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.6.1097
更新日期:1983-06-01 00:00:00
abstract::The gene encoding the SNF5/Ini1 core subunit of the SWI/SNF chromatin remodeling complex is a tumor suppressor in humans and mice, with an essential role in early embryonic development. To investigate further the function of this gene, we have generated a Cre/lox-conditional mouse line. We demonstrate that Snf5 deleti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.7.2661-2674.2006
更新日期:2006-04-01 00:00:00
abstract::The retinoblastoma binding protein 1 (RBP1) appears to be an important factor in the repression of E2F-dependent transcription by the retinoblastoma protein (pRB) family. The recent identification of the breast carcinoma associated antigen (BCAA) as an RBP1-like protein led us to investigate its biological properties ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.5.1917-1931.2006
更新日期:2006-03-01 00:00:00
abstract::In the budding yeast Saccharomyces cerevisiae, Cdc37 is required for the productive formation of Cdc28-cyclin complexes. The cdc37-1 mutant arrests at Start with low levels of Cdc28 protein, which is predominantly unphosphorylated at Thr169, fails to bind cyclin, and has little protein kinase activity. We show here th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.3.749-754.2000
更新日期:2000-02-01 00:00:00
abstract::Transfection of C3H/10T1/2 cells with a c-myc gene resulted in the acquisition of responsiveness to transforming growth factor type beta. Cells transfected with an activated H-ras gene or an H-ras and c-myc gene, however, exhibited a transformed morphology and spontaneous soft-agar growth, a phenotype induced reversib...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.7.2649
更新日期:1987-07-01 00:00:00
abstract::In this report, we document an unusual mode of tissue-enriched gene expression that is primarily mediated by alternative and inefficient splicing. We have analyzed posttranscriptional regulation of the Drosophila erect wing gene, which provides a vital neuronal function and is essential for the formation of certain mu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.6.3998
更新日期:1999-06-01 00:00:00
abstract::Protein tyrosine kinases activate the STAT (signal transducer and activator of transcription) signaling pathway, which can play essential roles in cell differentiation, cell cycle control, and development. However, the potential role of the STAT signaling pathway in the induction of apoptosis remains unexplored. Here ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.9.5328
更新日期:1997-09-01 00:00:00
abstract::The gene coding for the most abundant antifreeze protein (AFP) in the winter flounder was placed downstream of the Drosophila melanogaster hsp70 promoter and introduced into the D. melanogaster germ line by P-element-mediated transformation. In each of six transgenic strains tested, heat shock treatment induced the ex...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.6.2188
更新日期:1987-06-01 00:00:00
abstract::Protein modification by SUMO conjugation has emerged to be an important regulatory event. Recently, the mechanisms through which SUMO elicits its effects on target proteins have been elucidated. One of these is the noncovalent association between SUMO and coregulatory proteins via SUMO interaction motifs (SIMs). We th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01510-09
更新日期:2010-05-01 00:00:00
abstract::Glucocorticoids are among the most potent and effective agents for treating inflammatory diseases and hematological cancers. However, subpopulations of patients are often resistant to steroid therapy, and determining the molecular mechanisms that contribute to glucocorticoid resistance is thus critical to addressing t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01151-12
更新日期:2013-05-01 00:00:00
abstract::The CYC1-239-O mutation in the yeast Saccharomyces cerevisiae produces a -His-Leu- replacement of the normal -Ala-Gly- sequence at amino acid positions 5 and 6, which lie within a dispensable region of iso-1-cytochrome c; this mutation can accommodate the formation of a hairpin structure at the corresponding site in t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.8.1839
更新日期:1985-08-01 00:00:00
abstract::In both tissue sections and cell culture, the endothelial nature of a cell is most commonly determined by demonstration of its expression of von Willebrand factor (vWf) protein and/or mRNA. Thus, the mechanism of cell-type-specific transcriptional regulation of the vWf gene is central to studying the basis of endothel...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.2.999
更新日期:1994-02-01 00:00:00
abstract::The active beta-globin genes in chicken erythrocytes, like all active genes, reside in large chromatin domains which are preferentially sensitive to digestion by DNase I. We have recently proposed that the special structure of chromatin in active domains is maintained by torsional stress in the DNA (Villeponteau et al...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.5.1917
更新日期:1987-05-01 00:00:00
abstract::Histone methylation at H3K4 and H3K36 is commonly associated with genes actively transcribed by RNA polymerase II (RNAPII) and is catalyzed by Saccharomyces cerevisiae Set1 and Set2, respectively. Here we report that both methyltransferases can be UV cross-linked to RNA in vivo High-throughput sequencing of the bound ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00165-17
更新日期:2017-06-29 00:00:00
abstract::In cystic fibrosis (CF), epithelial cells are unable to normally up-regulate apical membrane Cl- secretion in response to agents which increase cyclic AMP, but they do increase Cl- secretion in response to increases in intracellular Ca2+. Since intracellular divalent cations regulate the expression of many genes, we h...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.4.1872
更新日期:1992-04-01 00:00:00