Abstract:
:Class Ia phosphatidylinositol 3 kinase (PI3K) is required for oncogenic receptor-mediated transformation; however, the individual roles of the two commonly expressed class Ia PI3K isoforms in oncogenic receptor signaling have not been elucidated in vivo. Here, we show that genetic ablation of p110α blocks tumor formation in both polyoma middle T antigen (MT) and HER2/Neu transgenic models of breast cancer. Surprisingly, p110β ablation results in both increased ductal branching and tumorigenesis. Biochemical analyses suggest a competition model in which the less active p110β competes with the more active p110α for receptor binding sites, thereby modulating the level of PI3K activity associated with activated receptors. Our findings demonstrate a novel p110β-based regulatory role in receptor-mediated PI3K activity and identify p110α as an important target for treatment of HER2-positive disease.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Utermark T,Rao T,Cheng H,Wang Q,Lee SH,Wang ZC,Iglehart JD,Roberts TM,Muller WJ,Zhao JJdoi
10.1101/gad.191973.112subject
Has Abstractpub_date
2012-07-15 00:00:00pages
1573-86issue
14eissn
0890-9369issn
1549-5477pii
26/14/1573journal_volume
26pub_type
杂志文章abstract::Treatment with retinoic acid (RA) is known to produce complex teratogenic effects in vertebrates, and its presence in the developing embryo as an endogenous substance has led to the suggestion that RA might be a natural morphogenetic agent. Although our understanding of the molecular mechanism of RA action has improve...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.8.1333
更新日期:1991-08-01 00:00:00
abstract::Cancer stem cells (CSCs) are postulated to be a small subset of tumor cells with tumor-initiating ability that shares features with normal tissue-specific stem cells. The origin of CSCs and the mechanisms underlying their genesis are poorly understood, and it is uncertain whether it is possible to obliterate CSCs with...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.171959.111
更新日期:2011-12-15 00:00:00
abstract::The N-myc gene encodes a putative transcription factor that is thought to function in the regulation of gene expression during cell differentiation and/or growth. To examine the role of N-myc during development, we have used targeted mutagenesis in embryonic stem cells to produce a mouse line that carries an N-myc nul...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.12a.2248
更新日期:1992-12-01 00:00:00
abstract::Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific an...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1267105
更新日期:2005-02-15 00:00:00
abstract::Coliphage N4 is a double-stranded DNA virus that requires the sequential activity of three different RNA polymerases during infection. The N4 virion RNA polymerase, which is carried in the virion and is injected with the DNA at the start of infection, is responsible for the synthesis of N4 early RNAs. In vitro, the vi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.10.2010
更新日期:1992-10-01 00:00:00
abstract::C-factor, the product of the csgA gene, is a cell-surface associated short-range intercellular signaling protein in Myxococcus xanthus. C-factor is required for at least four responses during starvation-induced fruiting body morphogenesis: rippling, aggregation, sporulation, and full expression of the csgA gene, all o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.6.740
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abstract::The Agrobacterium Ti plasmid (T-DNA) 6b proteins interact with many different host proteins implicated in plant cell proliferation. Here, we show that Arabidopsis plants overexpressing 6b display microRNA (miRNA) deficiency by directly targeting SERRATE and AGO1 via a specific loop fragment (residues 40-55). In additi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1985511
更新日期:2011-01-01 00:00:00
abstract::Cyclin B3 has been conserved during higher eukaryote evolution as evidenced by its identification in chicken, nematodes, and insects. We demonstrate that Cyclin B3 is present in addition to Cyclins A and B in mitotically proliferating cells and not detectable in endoreduplicating tissues of Drosophila embryos. Cyclin ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.23.3741
更新日期:1998-12-01 00:00:00
abstract::The ability to initiate organs throughout the lifecycle is a unique feature of plant development that is executed by groups of stem cells called meristems. The balance between stem cell proliferation and organ initiation is carefully regulated and ensures that organs can be initiated in regular geometric patterns. To ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.208501
更新日期:2001-10-15 00:00:00
abstract::Dosage compensation in Drosophila occurs by a twofold increase in transcription per copy of X-linked genes in males (XY) compared with females (XX). msl-1 is one of four genes that are essential for dosage compensation in males, and MSL-1 protein is associated specifically with the male X chromosome. To explore the ba...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.6.698
更新日期:1994-03-15 00:00:00
abstract::Hedgehog signaling has been linked to cell proliferation in a variety of systems; however, its effects on the cell cycle have not been closely studied. In the vertebrate retina, Hedgehog's effects are controversial, with some reports emphasizing increased proliferation and others pointing to a role in cell cycle exit....
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.391106
更新日期:2006-11-01 00:00:00
abstract::Bistability in developmental pathways refers to the generation of binary outputs from graded or noisy inputs. Signaling thresholds are critical for bistability. Specification of the left/right (LR) axis in vertebrate embryos involves bistable expression of transforming growth factor beta (TGFbeta) member NODAL in the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1682108
更新日期:2008-11-01 00:00:00
abstract::Export to the cytoplasm of U3 RNA transcribed from a rat U3 gene injected into the nucleus of Xenopus oocytes indicates that the biogenesis of U3 RNA, like that of the previously studied Sm-precipitable nucleoplasmic snRNAs (U1, U2, U4, and U5), includes a cytoplasmic phase. The regulation of import of the U3 snRNA in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.1120
更新日期:1992-06-01 00:00:00
abstract::The Hox gene products are transcription factors involved in specifying regional identity along the anteroposterior body axis. In the mouse, several single mutants for Hox genes show variably penetrant, partial homeotic transformations of vertebrae at their anterior limits of expression, suggesting that compound Hox mu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.13.1667
更新日期:1995-07-01 00:00:00
abstract::Symbiotic nitrogen fixation involves the development of specialized organs called nodules within which plant photosynthates are exchanged for combined nitrogen of bacterial origin. To determine the importance of bacterial nitrogen metabolism in symbiosis, we have characterized a key regulator of this metabolism in Rhi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.9.1194
更新日期:1997-05-01 00:00:00
abstract::The labial (lab) gene of Drosophila melanogaster is necessary for the proper development of the embryonic (larval) and adult head. We have identified the lab transcription unit within the proximal portion of the Antennapedia Complex (ANT-C) by mapping the molecular lesions associated with chromosomally rearranged lab ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.3.399
更新日期:1989-03-01 00:00:00
abstract::How muscle diversity is generated in the vertebrate body is poorly understood. In the limb, dorsal and ventral muscle masses constitute the first myogenic diversification, as each gives rise to distinct muscles. Myogenesis initiates after muscle precursor cells (MPCs) have migrated from the somites to the limb bud and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.187807.112
更新日期:2012-09-15 00:00:00
abstract::The mechanisms by which homeoproteins bind selectively to target genes in vivo have long remained unresolved. Here we report that PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein by regulating its subnuclear localization and proximity to target genes. We demonstrate that the interaction of Msx1 with PIAS...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1392006
更新日期:2006-04-01 00:00:00
abstract::A powerful enhancer has been mapped to an 18-bp DNA segment located 11 kb 5' to the human epsilon-globin gene within the dominant control or locus-activating region. This enhancer is inducible in K562 human erythroleukemia cells, increasing linked gamma-globin promoter/luciferase gene expression to 170-fold over an en...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.6.993
更新日期:1990-06-01 00:00:00
abstract::Mediator was resolved from yeast as a multiprotein complex on the basis of its requirement for transcriptional activation in a fully defined system. Three groups of mediator polypeptides could be distinguished: the products of five SRB genes, identified as suppressors of carboxy-terminal domain (CTD)-truncation mutant...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.1.45
更新日期:1998-01-01 00:00:00
abstract::Dendrite arborization patterns are critical determinants of neuronal function. To explore the basis of transcriptional regulation in dendrite pattern formation, we used RNA interference (RNAi) to screen 730 transcriptional regulators and identified 78 genes involved in patterning the stereotyped dendritic arbors of cl...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1391006
更新日期:2006-04-01 00:00:00
abstract::Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell-specific deletion of Max has a modest effect on B-cell development but completely abrogates Eµ-Myc-driven lymphomagenesis. While Max loss affects only a few hund...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.325878.119
更新日期:2019-09-01 00:00:00
abstract::Mice carrying a germ-line null mutation of the prolactin receptor gene have been produced by gene targeting in embryonic stem cells. Heterozygous females showed almost complete failure of lactation attributable to greatly reduced mammary gland development after their first, but not subsequent, pregnancies. Homozygous ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.2.167
更新日期:1997-01-15 00:00:00
abstract::The recombinational enhancer of the Hin inversion system in Salmonella stimulates recombination in vitro 150-fold in the presence of the Escherichia coli host factor Fis. To gain an understanding of the roles of the enhancer and Fis in stimulating the Hin-mediated inversion reaction, we have used nuclease and chemical...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.8.762
更新日期:1987-10-01 00:00:00
abstract::Binding of microRNA (miRNA) to mRNA within the RNA-induced silencing complex (RISC) leads to either translational inhibition or to destruction of the target mRNA. Both of these functions are executed by Argonaute 2 (Ago2). Using hematopoiesis in mice as a model system to study the physiological function of Ago2 in viv...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1565607
更新日期:2007-08-15 00:00:00
abstract::The mammary tumor-associated proto-oncogene Wnt-1/int-1 encodes a secreted protein implicated in the regulation of neural development in vertebrates and segmental pattern in Drosophila. Using a PCR-based strategy, we isolated cDNAs encoding six novel, related proteins that are expressed in fetal mice. Predicted protei...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.12b.2319
更新日期:1990-12-01 00:00:00
abstract::Members of the metazoan nuclear receptor superfamily regulate gene expression programs in response to binding of cognate lipophilic ligands. Evolutionary studies using bioinformatics tools have concluded that lower eukaryotes, such as fungi, lack nuclear receptor homologs. Here we review recent discoveries suggesting ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1743009
更新日期:2009-02-15 00:00:00
abstract::DOCK180 is involved in integrin signaling through CrkII-p130(Cas) complexes. We have studied the involvement of DOCK180 in Rac1 signaling cascades. DOCK180 activated JNK in a manner dependent on Rac1, Cdc42Hs, and SEK, and overexpression of DOCK180 increased the amount of GTP-bound Rac1 in 293T cells. Coexpression of ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.21.3331
更新日期:1998-11-01 00:00:00
abstract::Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differenti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237149.113
更新日期:2014-05-01 00:00:00
abstract::A complex array of genetic factors regulates neuronal dendrite morphology. Epigenetic regulation of gene expression represents a plausible mechanism to control pathways responsible for specific dendritic arbor shapes. By studying the Drosophila dendritic arborization (da) neurons, we discovered a role of the double-br...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.239962.114
更新日期:2014-09-01 00:00:00