AP-1 complexes containing cJun and JunB cause cellular transformation of Rat1a fibroblasts and share transcriptional targets.

Abstract:

:To investigate the role of individual Jun proteins in cell growth and transformation, we have used a doxycycline-inducible retroviral vector to regulate their expression in rat fibroblasts. AP-1 complexes enriched with cJun and JunB result in morphological alterations and anchorage-independent cell growth consistent with a transformation-like phenotype, whereas complexes enriched with JunD had an antiproliferative effect. These results suggest that genes regulated by both cJun and JunB are potentially involved in transformation and that they can be distinguished from those regulated by AP-1 complexes containing JunD. To identify genes regulated by cJun and JunB that may have a role in anchorage-independent growth, we investigated differential gene expression by each of the Jun family members using the Affymetrix Rat oligonucleotide microarray, RG_U34A containing approximately 8000 genes. Differentially regulated genes were identified and grouped for correlation with regulation by the different Jun proteins. A total of 33 candidate genes were found to be differentially regulated by both cJun and JunB and not by JunD. These genes have roles in cell metabolism, growth, signal transduction, migration and adhesion. We validated the differential regulation by cJun and JunB of 10 candidate genes by Northern blot analysis. Of these, eight were further characterized as potential direct targets of AP-1 regulation based on Northern blot results showing differential regulation that correlate with cJun expression. Our results show that inducible cJun and JunB expression result in anchorage-independent growth of Rat1a cells, distinct from JunD-expressing cells. This model system and a functional genomic approach enabled us to differentiate AP-1-regulated genes involved in transformation from AP-1-regulated genes known as bystander genes. This approach significantly reduces the number of bystanders and allows for the targeting of genes specifically involved in transformation.

journal_name

Oncogene

journal_title

Oncogene

authors

Leaner VD,Kinoshita I,Birrer MJ

doi

10.1038/sj.onc.1206644

subject

Has Abstract

pub_date

2003-08-28 00:00:00

pages

5619-29

issue

36

eissn

0950-9232

issn

1476-5594

pii

1206644

journal_volume

22

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Signaling coupled epigenomic regulation of gene expression.

    abstract::Inheritance of genomic information independent of the DNA sequence, the epigenetics, as well as gene transcription are profoundly shaped by serine/threonine and tyrosine signaling kinases and components of the chromatin remodeling complexes. To precisely respond to a changing external milieu, human cells efficiently t...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2017.201

    authors: Kumar R,Deivendran S,Santhoshkumar TR,Pillai MR

    更新日期:2017-10-26 00:00:00

  • Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis.

    abstract::We have previously shown that tumor necrosis factor (TNF)α produced from primary tumor-induced expression of two endogenous Toll-like receptor 4 (TLR4) ligands, S100A8 and serum amyloid A3 (SAA3), in pre-metastatic lungs. However, mechanistic details of the signaling network and relevance to pulmonary physiology are p...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.53

    authors: Tomita T,Sakurai Y,Ishibashi S,Maru Y

    更新日期:2011-08-04 00:00:00

  • The non-catalytic domain of ras-GAP inhibits transformation induced by G protein coupled receptors.

    abstract::We have studied the relationship between ras-GAP and G protein coupled receptors in a proliferative setting comprised of NIH3T3 expressing transfected muscarinic receptors (mAChRs). GAP expression plasmids were engineered to encode wild-type GAP, its carboxyl-terminal catalytic domain, a mutant lacking a portion of th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Xu N,McCormick F,Gutkind JS

    更新日期:1994-02-01 00:00:00

  • Infrequent alteration of the c-myc gene in human glial tumours associated with increased numbers of c-myc positive cells.

    abstract::Twenty five human glial tumours of different grades of malignancy were examined by Southern blotting and polymerase chain reaction (PCR) for alterations (rearrangements, amplification and deletions) in the c-myc gene. Number of c-myc positive cells per thousand cells were also counted in all the tumours after immunohi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Chattopadhyay P,Banerjee M,Sarkar C,Mathur M,Mohapatra AK,Sinha S

    更新日期:1995-12-21 00:00:00

  • IL-17C mediates the recruitment of tumor-associated neutrophils and lung tumor growth.

    abstract::Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for lung cancer and an aberrant microbiota of the lung. Microbial colonization contributes to chronic neutrophilic inflammation in COPD. Nontypeable Haemophilus influenzae (NTHi) is frequently found in lungs of stable COPD patients and i...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.28

    authors: Jungnickel C,Schmidt LH,Bittigkoffer L,Wolf L,Wolf A,Ritzmann F,Kamyschnikow A,Herr C,Menger MD,Spieker T,Wiewrodt R,Bals R,Beisswenger C

    更新日期:2017-07-20 00:00:00

  • Heparan sulphate proteoglycans are essential for the myeloma cell growth activity of EGF-family ligands in multiple myeloma.

    abstract::The epidermal growth factor (EGF)/EGF-receptor (ErbB1-4) family is involved in the biology of multiple myeloma (MM). In particular, ErbB-specific inhibitors induce strong apoptosis of myeloma cells (MMC) in vitro. To delineate the contribution of the 10 EGF-family ligands to the pathogenesis of MM, we have assessed th...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209699

    authors: Mahtouk K,Cremer FW,Rème T,Jourdan M,Baudard M,Moreaux J,Requirand G,Fiol G,De Vos J,Moos M,Quittet P,Goldschmidt H,Rossi JF,Hose D,Klein B

    更新日期:2006-11-16 00:00:00

  • Targeting AU-rich element-mediated mRNA decay with a truncated active form of the zinc-finger protein TIS11b/BRF1 impairs major hallmarks of mammary tumorigenesis.

    abstract::Altered expression of regulatory RNA-binding proteins (RBPs) in cancer leads to abnormal expression of mRNAs encoding many factors involved in cancer hallmarks. While conventional anticancer therapies usually target one pathway at a time, targeting key RBP would affect multiple genes and thus overcome drug resistance....

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0784-8

    authors: Rataj F,Planel S,Denis J,Roelants C,Filhol O,Guyon L,Feige JJ,Cherradi N

    更新日期:2019-06-01 00:00:00

  • Structure, expression, and activity of Tyro 3, a neural adhesion-related receptor tyrosine kinase.

    abstract::We have isolated mouse cDNA clones encoding Tyro 3, a receptor protein-tyrosine kinase (PTK) of the mammalin central nervous system (CNS). Expression of the Tyro 3 gene is strongly up-regulated in neurons of the mouse neocortex, cerebellum, and hippocampus after the day of birth, during periods of active synaptogenesi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Lai C,Gore M,Lemke G

    更新日期:1994-09-01 00:00:00

  • Correction: Epigenetic loss of AOX1 expression via EZH2 leads to metabolic deregulations and promotes bladder cancer progression.

    abstract::After publication of this Article, the Authors noticed errors in some of the Figures. In Figures 2e, 2f-g, 4a, 4j, 5a and 6b, unmatched β-actin was inadvertently used as loading control for the immunoblots. These have been corrected using repeat data from a similar set of samples and the revised Figures containing mat...

    journal_title:Oncogene

    pub_type: 已发布勘误

    doi:10.1038/s41388-020-1283-7

    authors: Vantaku V,Putluri V,Bader DA,Maity S,Ma J,Arnold JM,Rajapakshe K,Donepudi SR,von Rundstedt FC,Devarakonda V,Dubrulle J,Karanam B,McGuire SE,Stossi F,Jain AK,Coarfa C,Cao Q,Sikora AG,Villanueva H,Kavuri SM,Lotan Y

    更新日期:2020-10-01 00:00:00

  • The chicken Pdcd4 gene is regulated by v-Myb.

    abstract::The retroviral oncogene v-myb encodes a transcription factor (v-Myb) which is responsible for the ability of avian myeloblastosis virus (AMV) to transform myelomonocytic cells. v-Myb is thought to disrupt the differentiation of myelomonocytic cells by affecting the expression of specific target genes. To identify such...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204071

    authors: Schlichter U,Burk O,Worpenberg S,Klempnauer KH

    更新日期:2001-01-11 00:00:00

  • Hepatitis B virus X protein induces the expression of MTA1 and HDAC1, which enhances hypoxia signaling in hepatocellular carcinoma cells.

    abstract::Expression level of metastasis-associated protein 1 (MTA1) is closely related to tumor growth and metastasis in various cancers. Although increased expression level of MTA1 was observed in hepatocellular carcinoma (HCC), role of MTA1 complex containing histone deacetylase (HDAC) in hepatitis B virus (HBV)-associated h...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1211000

    authors: Yoo YG,Na TY,Seo HW,Seong JK,Park CK,Shin YK,Lee MO

    更新日期:2008-05-29 00:00:00

  • Transcriptional and post-transcriptional induction of the TGFalpha gene in transformed rat liver epithelial cells.

    abstract::Although TGFalpha mRNA and protein are frequently elevated in neoplastic cells, neither the level at which deregulation occurs nor the mechanism(s) responsible have been well characterized. As a first step, we examined the induction of TGFalpha mRNA in two series of clonally-derived rat liver epithelial cell lines tha...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Berkowitz EA,Hissong MA,Lee DC

    更新日期:1996-05-02 00:00:00

  • The neural guidance receptor Plexin C1 delays melanoma progression.

    abstract::Plexin C1 is a type I transmembrane receptor with intrinsic R-Ras GTPase activity, which regulates cytoskeletal remodeling and adhesion in normal human melanocytes. Melanocytes are pigment-producing cells of the epidermis, precursors for melanoma, and express high levels of Plexin C1, which is lost in melanoma in vitr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.511

    authors: Chen Y,Soong J,Mohanty S,Xu L,Scott G

    更新日期:2013-10-10 00:00:00

  • Functional interactions within adenovirus E1A protein complexes.

    abstract::The transforming potential of adenovirus E1A oncogene products derives largely from the formation of complexes with cellular proteins, including the p105Rb tumor suppressor and a related p107 species, p130 and p300 proteins, and cyclin A (p60cycA). Extensive quantitative analyses using E1A deletion mutants identified ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Barbeau D,Charbonneau R,Whalen SG,Bayley ST,Branton PE

    更新日期:1994-02-01 00:00:00

  • The role of Gads in hematopoietic cell signalling.

    abstract::Gads is a member of the family of SH2 and SH3 domain containing adaptor proteins that is expressed specifically in hematopoietic cells and functions in the coordination of tyrosine kinase mediated signal transduction. Gads plays a critical role in signalling from the T cell receptor by promoting the formation of a com...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1204771

    authors: Liu SK,Berry DM,McGlade CJ

    更新日期:2001-10-01 00:00:00

  • The VHL tumor suppressor inhibits expression of the IGF1R and its loss induces IGF1R upregulation in human clear cell renal carcinoma.

    abstract::Clear cell renal cell cancer (CC-RCC) is a highly chemoresistant tumor characterized by frequent inactivation of the von Hippel-Lindau (VHL) gene. The prognosis is reportedly worse in patients whose tumors express immunoreactive type I insulin-like growth factor receptor (IGF1R), a key mediator of tumor cell survival....

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210474

    authors: Yuen JS,Cockman ME,Sullivan M,Protheroe A,Turner GD,Roberts IS,Pugh CW,Werner H,Macaulay VM

    更新日期:2007-10-04 00:00:00

  • Overexpression of c-fos in a human pre-B cell acute lymphocytic leukemia derived cell line, SMS-SB.

    abstract::The c-fos proto-oncogene is found to be overexpressed at least 30-fold in SMS-SB, a pre-B leukemic cell line compared to other cell types. No gross alteration of the c-fos gene structure in SMS-SB cells can be detected by karyotypic or Southern analyses. C-fos in SMS-SB cells can still be induced by serum, TPA and the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Tsai LH,Nanu L,Smith RG,Ozanne B

    更新日期:1991-01-01 00:00:00

  • Hyperactivation of EGFR and downstream effector phospholipase D1 by oncogenic FAM83B.

    abstract::Despite the progress made in targeted anticancer therapies in recent years, challenges remain. The identification of new potential targets will ensure that the arsenal of cancer therapies continues to expand. FAM83B was recently discovered in a forward genetic screen for novel oncogenes that drive human mammary epithe...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.293

    authors: Cipriano R,Bryson BL,Miskimen KL,Bartel CA,Hernandez-Sanchez W,Bruntz RC,Scott SA,Lindsley CW,Brown HA,Jackson MW

    更新日期:2014-06-19 00:00:00

  • Phosphorylation of integrin in differentiating ts-Rous sarcoma virus-infected myogenic cells.

    abstract::The differentiation of primary myogenic cultures requires the attachment of the cells to an extracellular matrix substrate using an integrin family receptor. These integrin receptors can be phosphorylated on both their alpha and beta chains, and it has been postulated that phosphorylation regulates the receptor functi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Aneskievich BJ,Haimovich B,Boettiger D

    更新日期:1991-08-01 00:00:00

  • How do K-RAS-activated cells evade cellular defense mechanisms?

    abstract::Lung adenocarcinomas, like other cancers, develop through the accumulation of epigenetic and genetic alterations. Numerous studies have shown that K-RAS mutation is among the most important early events in carcinogenesis of the lung. However, it is also well established that growth-stimulating signals feed back into g...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2015.153

    authors: Lee YS,Bae SC

    更新日期:2016-02-18 00:00:00

  • Phosphorylation at serine 28 and acetylation at lysine 9 of histone H3 induced by trichostatin A.

    abstract::Trichostatin A (TSA), a histone deacetylase inhibitor, strongly increases acetylation of the N-terminal tails of histone H3. Many studies have correlated the function of TSA with the hyperacetylation of histone. Although histone H3 is known to be phosphorylated, the effect of acetylation on phosphorylation is not know...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206507

    authors: Zhong S,Goto H,Inagaki M,Dong Z

    更新日期:2003-08-14 00:00:00

  • Growth stimulation of murine fibroblasts by TGF-beta1 depends on the expression of a functional p53 protein.

    abstract::Transforming Growth Factor-beta1 (TGF-beta1) inhibits the proliferation of most cells, but stimulates some mesenchymal cell types, including murine NIH3T3 fibroblasts. We show here that TGF-beta1 growth stimulation of NIH3T3 fibroblasts is reversed when these cells are transformed by SV40 or are transfected with a pla...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202341

    authors: Dkhissi F,Raynal S,Jullien P,Lawrence DA

    更新日期:1999-01-21 00:00:00

  • Interaction of HTLV-1 Tax and methyl-CpG-binding domain 2 positively regulates the gene expression from the hypermethylated LTR.

    abstract::Epigenetic regulation of gene expression is critical in the maintenance of cellular homeostasis. Dysregulation of normal epigenetic transcription occurs in abnormal physiological conditions, such as those seen in cancer cells and cells infected with parasites, making the mechanism underlying abnormal epigenetic transc...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208394

    authors: Ego T,Tanaka Y,Shimotohno K

    更新日期:2005-03-10 00:00:00

  • Intestinal cancer progression by mutant p53 through the acquisition of invasiveness associated with complex glandular formation.

    abstract::Tumor suppressor TP53 is frequently mutated in colorectal cancer (CRC), and most mutations are missense type. Although gain-of-functions by mutant p53 have been demonstrated experimentally, the precise mechanism for malignant progression in in vivo tumors remains unsolved. We generated ApcΔ716 Trp53LSL•R270H villin-Cr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.194

    authors: Nakayama M,Sakai E,Echizen K,Yamada Y,Oshima H,Han TS,Ohki R,Fujii S,Ochiai A,Robine S,Voon DC,Tanaka T,Taketo MM,Oshima M

    更新日期:2017-10-19 00:00:00

  • Akt phosphorylates the Y-box binding protein 1 at Ser102 located in the cold shock domain and affects the anchorage-independent growth of breast cancer cells.

    abstract::Akt/PKB is a serine/threonine kinase that promotes tumor cell growth by phosphorylating transcription factors and cell cycle proteins. There is particular interest in finding tumor-specific substrates for Akt to understand how this protein functions in cancer and to provide new avenues for therapeutic targeting. Our l...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208590

    authors: Sutherland BW,Kucab J,Wu J,Lee C,Cheang MC,Yorida E,Turbin D,Dedhar S,Nelson C,Pollak M,Leighton Grimes H,Miller K,Badve S,Huntsman D,Blake-Gilks C,Chen M,Pallen CJ,Dunn SE

    更新日期:2005-06-16 00:00:00

  • Cloning, expression and chromosomal localization of a novel gene for protein tyrosine phosphatase (PTP-U2) induced by various differentiation-inducing agents.

    abstract::Previously, we cloned two gene fragments encoding novel protein tyrosine phosphatases, termed PTP-U1 and PTP-U2. Here, we report the full-length sequence, expression, and chromosomal localization of the PTP-U2 gene. The cDNA for PTP-U2, which was obtained from a human normal kidney library, predicts a protein of 1216 ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Seimiya H,Sawabe T,Inazawa J,Tsuruo T

    更新日期:1995-05-04 00:00:00

  • Epstein-Barr virus latent membrane protein-1 (LMP1) signalling is distinct from CD40 and involves physical cooperation of its two C-terminus functional regions.

    abstract::The Epstein-Barr virus (EBV) encoded Latent Membrane Protein-1 (LMP1) mimics a constitutively active receptor molecule, and has been shown to activate NF-kappaB and the MAPK and JNK pathways. Two regions within the cytosolic domain of LMP1 have been found to effect cell signalling. One of these, the carboxy-terminal a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202144

    authors: Floettmann JE,Eliopoulos AG,Jones M,Young LS,Rowe M

    更新日期:1998-11-05 00:00:00

  • Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo.

    abstract::Delta(9)-Tetrahydrocannabinol (THC) is the primary cannabinoid of marijuana and has been shown to either potentiate or inhibit tumor growth, depending on the type of cancer and its pathogenesis. Little is known about the activity of cannabinoids like THC on epidermal growth factor receptor-overexpressing lung cancers,...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210641

    authors: Preet A,Ganju RK,Groopman JE

    更新日期:2008-01-10 00:00:00

  • The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family.

    abstract::Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the end...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2008.309

    authors: Heath-Engel HM,Chang NC,Shore GC

    更新日期:2008-10-27 00:00:00

  • Protein interactions at Sp1-like sites in the TGF alpha promoter as visualized by in vivo genomic footprinting.

    abstract::Transcription from the rat TGF alpha promoter initiates at two predominant sites (-188 and -58) in a G+C-rich region that does not contain TATA or CAAT motifs. Previous studies using transfected reporter constructs implicated the transcription factor Sp1 in active expression from the promoter, particularly from the -5...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Chen X,Wright KL,Berkowitz EA,Azizkhan JC,Ting JP,Lee DC

    更新日期:1994-11-01 00:00:00