Ras-mediated suppression of TGFbetaRII expression in intestinal epithelial cells involves Raf-independent signaling.

Abstract:

:Ras-transformed intestinal epithelial cells are resistant to the growth inhibitory actions of TGFbeta and have a marked decrease in expression of the TGFbeta type II receptor (TGFbetaRII). Rat intestinal epithelial cells (RIE) were stably transfected with activated Ras, Sos and Raf constructs and tested for expression of TGFbetaRII and sensitivity to growth inhibition by TGFbeta. The parental RIE line and the RIE-Raf cells were non-transformed in morphology and were sensitive to TGFbeta (70-90% inhibited). In contrast, the RIE-Ras and RIE-Sos lines were transformed, resistant to TGFbeta and expressed 5- to 10-fold decreased levels of the TGFbetaRII mRNA and protein. Cyclin D1 protein expression was repressed by TGFbeta treatment in parental RIE and RIE-Raf cells, whereas levels of cyclin D1 in RIE-Ras and RIE-Sos cells remained unchanged. Treatment of RIE-Ras cells with 25 microM farnesyl transferase inhibitor, FTI L739,749, for 48 hours restored expression of TGFbetaRII to levels equivalent to control cells. In addition, treatment of RIE-Ras cells for 48 hours with PD-98059, a specific MAPKK inhibitor, also increased expression of TGFbetaRII to control levels. Collectively these results suggest that downregulation of TGFbetaRII and loss of sensitivity to growth inhibition by TGFbeta in Ras-transformed intestinal epithelial cells is not mediated exclusively by the conventional Ras/Raf/MAPKK/MAPK pathway. However, activation of MAPK, perhaps by an alternate Ras effector pathway, appears to be necessary for Ras-mediated downregulation of TGFbetaRII.

journal_name

Neoplasia

authors

Bulus NM,Sheng HM,Sizemore N,Oldham SM,Barnett JV,Coffey RJ,Beauchamp DR,Barnard JA

doi

10.1038/sj.neo.7900099

keywords:

subject

Has Abstract

pub_date

2000-07-01 00:00:00

pages

357-64

issue

4

eissn

1522-8002

issn

1476-5586

journal_volume

2

pub_type

杂志文章
  • Detection of hypoxia in human brain tumor xenografts using a modified comet assay.

    abstract::We used the standard comet assay successfully to generate in vitro dose-response curves under oxic and hypoxic conditions. We then made mixtures of cells that had been irradiated with 3 and 9 Gy of X-rays to simulate two subpopulations in a tumor, but efforts to accurately detect and quantify the subpopulations using ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/S1476-5586(03)80022-2

    authors: Wang J,Klem J,Wyrick JB,Ozawa T,Cunningham E,Golinveaux J,Allen MJ,Lamborn KR,Deen DF

    更新日期:2003-07-01 00:00:00

  • Role of the TMPRSS2-ERG gene fusion in prostate cancer.

    abstract::TMPRSS2-ERG gene fusions are the predominant molecular subtype of prostate cancer. Here, we explored the role of TMPRSS2-ERG gene fusion product using in vitro and in vivo model systems. Transgenic mice expressing the ERG gene fusion product under androgen-regulation develop mouse prostatic intraepithelial neoplasia (...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07822

    authors: Tomlins SA,Laxman B,Varambally S,Cao X,Yu J,Helgeson BE,Cao Q,Prensner JR,Rubin MA,Shah RB,Mehra R,Chinnaiyan AM

    更新日期:2008-02-01 00:00:00

  • Neoplastic transformation induced by the gep oncogenes involves the scaffold protein JNK-interacting leucine zipper protein.

    abstract::The activated mutants of the α-subunits of G proteins G(12) and G(13) have been designated as the gep oncogenes owing to their ability to stimulate diverse oncogenic signaling pathways that lead to neoplastic transformation of fibroblast cell lines and tumorigenesis in nude mice models. Studies from our laboratory as ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.101622

    authors: Kashef K,Radhakrishnan R,Lee CM,Reddy EP,Dhanasekaran DN

    更新日期:2011-04-01 00:00:00

  • Dinosaurs and ancient civilizations: reflections on the treatment of cancer.

    abstract::Research efforts in the area of palaeopathology have been seen as an avenue to improve our understanding of the pathogenesis of cancer. Answers to questions of whether dinosaurs had cancer, or if cancer plagued ancient civilizations, have captured the imagination as well as the popular media. Evidence for dinosaurian ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 历史文章,杂志文章

    doi:10.1593/neo.101588

    authors: Rehemtulla A

    更新日期:2010-12-01 00:00:00

  • Distinct patterns of structural and numerical chromosomal instability characterize sporadic ovarian cancer.

    abstract::Sporadic ovarian cancer is a particularly aggressive tumor characterized by highly abnormal karyotypes exhibiting many features of genomic instability. More complex genomic changes in tumors arise as a consequence of chromosomal instability (CIN), which can generate both numerical [(N)-CIN] and structural chromosomal ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.08584

    authors: Bayani J,Paderova J,Murphy J,Rosen B,Zielenska M,Squire JA

    更新日期:2008-10-01 00:00:00

  • Association of the actin-binding protein transgelin with lymph node metastasis in human colorectal cancer.

    abstract::Metastatic dissemination of primary tumors is responsible for 90% of colorectal cancer (CRC) deaths. The presence of positive lymph nodes, which separates stage I/II from stage III CRC, is a particularly key factor in patient management. Here, we describe results of a quantitative proteomic survey to identify molecula...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.09542

    authors: Lin Y,Buckhaults PJ,Lee JR,Xiong H,Farrell C,Podolsky RH,Schade RR,Dynan WS

    更新日期:2009-09-01 00:00:00

  • Antibody-dependent cell-mediated cytotoxicity effector-enhanced EphA2 agonist monoclonal antibody demonstrates potent activity against human tumors.

    abstract::EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vi...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.81578

    authors: Bruckheimer EM,Fazenbaker CA,Gallagher S,Mulgrew K,Fuhrmann S,Coffman KT,Walsh W,Ready S,Cook K,Damschroder M,Kinch M,Kiener PA,Woods R,Gao C,Dall'Acqua W,Wu H,Coats S

    更新日期:2009-06-01 00:00:00

  • A novel topoisomerase inhibitor, daurinol, suppresses growth of HCT116 cells with low hematological toxicity compared to etoposide.

    abstract::We report that daurinol, a novel arylnaphthalene lignan, is a promising potential anticancer agent with adverse effects that are less severe than those of etoposide, a clinical anticancer agent. Despite its potent antitumor activity, clinical use of etoposide is limited because of its adverse effects, including myelos...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.11972

    authors: Kang K,Oh SH,Yun JH,Jho EH,Kang JH,Batsuren D,Tunsag J,Park KH,Kim M,Nho CW

    更新日期:2011-11-01 00:00:00

  • The effects of a novel MEK inhibitor PD184161 on MEK-ERK signaling and growth in human liver cancer.

    abstract::The MEK-ERK growth signaling pathway is important in human hepatocellular carcinoma (HCC). To evaluate the targeting of this pathway in HCC, we characterized a novel, orally-active MEK inhibitor, PD184161, using human HCC cells (HepG2, Hep3B, PLC, and SKHep) and in vivo human tumor xenografts. PD184161 inhibited MEK a...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.05373

    authors: Klein PJ,Schmidt CM,Wiesenauer CA,Choi JN,Gage EA,Yip-Schneider MT,Wiebke EA,Wang Y,Omer C,Sebolt-Leopold JS

    更新日期:2006-01-01 00:00:00

  • ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5.

    abstract::The ZNF198- FGFR1 fusion gene arises as a result of the t(8;13)(p11;q12) in the 8p11 myeloproliferative syndrome. To determine the transforming properties of this chimeric protein we transfected ZNF198-FGFR1 into the interleukin (IL)-3 dependent cell line Ba/F3. Growth factor independent subclones were obtained in whi...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900035

    authors: Smedley D,Demiroglu A,Abdul-Rauf M,Heath C,Cooper C,Shipley J,Cross NC

    更新日期:1999-10-01 00:00:00

  • Characterization and Targeting of Platelet-Derived Growth Factor Receptor alpha (PDGFRA) in Inflammatory Breast Cancer (IBC).

    abstract:PURPOSE:Inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer due to its rapid onset and highly invasive nature. IBC carries 5- and 10-year disease-free survival rates of ~45% and <20%, respectively. Multiple studies demonstrate that in comparison with conventional breast cancer, IBC has a un...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2017.03.002

    authors: Joglekar-Javadekar M,Van Laere S,Bourne M,Moalwi M,Finetti P,Vermeulen PB,Birnbaum D,Dirix LY,Ueno N,Carter M,Rains J,Ramachandran A,Bertucci F,van Golen KL

    更新日期:2017-07-01 00:00:00

  • Identification and validation of commonly overexpressed genes in solid tumors by comparison of microarray data.

    abstract::Cancers originating from epithelial cells are the most common malignancies. No common expression profile of solid tumors compared to normal tissues has been described so far. Therefore we were interested if genes differentially expressed in the majority of carcinomas could be identified using bioinformatic methods. Co...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04277

    authors: Pilarsky C,Wenzig M,Specht T,Saeger HD,Grützmann R

    更新日期:2004-11-01 00:00:00

  • Diffusion-weighted magnetic resonance imaging allows noninvasive in vivo monitoring of the effects of combretastatin a-4 phosphate after repeated administration.

    abstract::The noninvasive assessment of anticancer treatment efficacy is very important for the improvement of therapeutic window. The purpose of the present study was to evaluate the antitumoral effects of the vascular targeting agent, combretastatin A-4 phosphate (CA-4-P), at selected time points after repeated intraperitonea...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.04748

    authors: Thoeny HC,De Keyzer F,Chen F,Vandecaveye V,Verbeken EK,Ahmed B,Sun X,Ni Y,Bosmans H,Hermans R,van Oosterom A,Marchal G,Landuyt W

    更新日期:2005-08-01 00:00:00

  • Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma.

    abstract::Wnt/beta-catenin signaling plays an important role in normal development. However, its aberrant activation is associated with several cancers. The aim of this study is to examine the Wnt/beta-catenin pathway in patients with advanced pancreatic adenocarcinoma (n = 31). Paraffin sections from tumors (n = 16) and normal...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.05607

    authors: Zeng G,Germinaro M,Micsenyi A,Monga NK,Bell A,Sood A,Malhotra V,Sood N,Midda V,Monga DK,Kokkinakis DM,Monga SP

    更新日期:2006-04-01 00:00:00

  • Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors.

    abstract::The epidermal growth factor receptor (EGFR) has been targeted for inhibition using tyrosine kinase inhibitors and monoclonal antibodies, with improvement in outcome in subsets of patients with head and neck, lung, and colorectal carcinomas. We have previously found that EGFR stability plays a key role in cell survival...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.12986

    authors: Ahsan A,Ramanand SG,Whitehead C,Hiniker SM,Rehemtulla A,Pratt WB,Jolly S,Gouveia C,Truong K,Van Waes C,Ray D,Lawrence TS,Nyati MK

    更新日期:2012-08-01 00:00:00

  • PODXL1 promotes metastasis of the pancreatic ductal adenocarcinoma by activating the C5aR/C5a axis from the tumor microenvironment.

    abstract::Pancreatic invasive ductal adenocarcinoma (PDAC) is a representative intractable malignancy under the current cancer therapies, and is considered a scirrhous carcinoma because it develops dense stroma. Both PODXL1, a member of CD34 family molecules, and C5aR, a critical cell motility inducer, have gained recent attent...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2019.09.003

    authors: Saito K,Iioka H,Maruyama S,Sumardika IW,Sakaguchi M,Kondo E

    更新日期:2019-12-01 00:00:00

  • ASPL-TFE3 Oncoprotein Regulates Cell Cycle Progression and Induces Cellular Senescence by Up-Regulating p21.

    abstract::Alveolar soft part sarcoma is an extremely rare soft tissue sarcoma with poor prognosis. It is characterized by the unbalanced recurrent chromosomal translocation der(17)t(X;17)(p11;q25), resulting in the generation of an ASPL-TFE3 fusion gene. ASPL-TFE3 oncoprotein functions as an aberrant transcriptional factor and ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2016.08.001

    authors: Ishiguro N,Yoshida H

    更新日期:2016-10-01 00:00:00

  • Tel, a frequent target of leukemic translocations, induces cellular aggregation and influences expression of extracellular matrix components.

    abstract::Tel is an Ets transcription factor that is the target of chromosome translocations in lymphoid and myeloid leukemias and in solid tumors. It contains two functional domains, a pointed oligomerization domain and a DNA-binding domain. Retroviral transduction of a wild-type Tel cDNA into a clonal subline of NIH3T3 fibrob...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900064

    authors: Van Rompaey L,Dou W,Buijs A,Grosveld G

    更新日期:1999-12-01 00:00:00

  • Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo.

    abstract::A noninvasive method for molecular imaging of T-cell activity in vivo would be of considerable value. It would aid in understanding the role of specific genes and signal transduction pathways in the course of normal and pathologic immune responses, and could elucidate temporal dynamics and immune regulation at differe...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1038/sj.neo.7900204

    authors: Ponomarev V,Doubrovin M,Lyddane C,Beresten T,Balatoni J,Bornman W,Finn R,Akhurst T,Larson S,Blasberg R,Sadelain M,Tjuvajev JG

    更新日期:2001-11-01 00:00:00

  • Cancer: A turbulence problem.

    abstract::Cancers are complex, adaptive ecosystems. They remain the leading cause of disease-related death among children in North America. As we approach computational oncology and Deep Learning Healthcare, our mathematical models of cancer dynamics must be revised. Recent findings support the perspective that cancer-microenvi...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章,评审

    doi:10.1016/j.neo.2020.09.008

    authors: Uthamacumaran A

    更新日期:2020-12-01 00:00:00

  • Concomitant BCORL1 and BRAF Mutations in Vemurafenib-Resistant Melanoma Cells.

    abstract::BRAF is the most frequently mutated gene in melanoma. Constitutive activation of mutant BRAFV600E leads to aberrant Ras-independent MAPK signaling and cell transformation. Inhibition of mutant BRAF is a current frontline therapy for such cases, with improved survival compared with chemotherapy. Unfortunately, reactiva...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2018.02.009

    authors: Mologni L,Costanza M,Sharma GG,Viltadi M,Massimino L,Citterio S,Purgante S,Raman H,Pirola A,Zucchetti M,Piazza R,Gambacorti-Passerini C

    更新日期:2018-05-01 00:00:00

  • Chronic pancreatitis and systemic inflammatory response syndrome prevent impact of chemotherapy with gemcitabine in a genetically engineered mouse model of pancreatic cancer.

    abstract:BACKGROUND AND AIMS:BACKGROUND AND AIMSGemcitabine is the standard therapy for patients with pancreatic cancer with metastatic disease. Patients with metastatic pancreatic cancer presenting with increased values of C-reactive protein do not respond to gemcitabine. So far, no studies have evaluated the correlation betwe...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.05.010

    authors: Knoop RF,Sparn M,Waldmann J,Plassmeier L,Bartsch DK,Lauth M,Hudemann C,Fendrich V

    更新日期:2014-06-01 00:00:00

  • CXCR4 regulates the early extravasation of metastatic tumor cells in vivo.

    abstract::Recent studies have demonstrated that the chemokine receptor CXCR4 plays a crucial role in organ-specific metastasis formation. Although a variety of studies showed the expression of chemokine receptors, in particular, CXCR4, by gastrointestinal tumors, the precise mechanisms of chemokine receptor-mediated homing of c...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.09272

    authors: Gassmann P,Haier J,Schlüter K,Domikowsky B,Wendel C,Wiesner U,Kubitza R,Engers R,Schneider SW,Homey B,Müller A

    更新日期:2009-07-01 00:00:00

  • Molecular characterization of TMPRSS2-ERG gene fusion in the NCI-H660 prostate cancer cell line: a new perspective for an old model.

    abstract::Recent studies have established that a significant fraction of prostate cancers harbor a signature gene fusion between the 5' region of androgen-regulated TMPRSS2 and an ETS family transcription factor, most commonly ERG. Studies on the molecular mechanisms and functional consequences of this important chromosomal rea...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.07103

    authors: Mertz KD,Setlur SR,Dhanasekaran SM,Demichelis F,Perner S,Tomlins S,Tchinda J,Laxman B,Vessella RL,Beroukhim R,Lee C,Chinnaiyan AM,Rubin MA

    更新日期:2007-03-01 00:00:00

  • The roles of telomerase in the generation of polyploidy during neoplastic cell growth.

    abstract::Polyploidy contributes to extensive intratumor genomic heterogeneity that characterizes advanced malignancies and is thought to limit the efficiency of current cancer therapies. It has been shown that telomere deprotection in p53-deficient mouse embryonic fibroblasts leads to high rates of polyploidization. We now sho...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.121398

    authors: Christodoulidou A,Raftopoulou C,Chiourea M,Papaioannou GK,Hoshiyama H,Wright WE,Shay JW,Gagos S

    更新日期:2013-02-01 00:00:00

  • Strain background determines lymphoma incidence in Atm knockout mice.

    abstract::About 10% to 30% of patients with ataxia-telangiectasia (A-T) develop leukemias or lymphomas. There is considerable interpatient variation in the age of onset and leukemia/lymphoma type. The incomplete penetrance and variable age of onset may be attributable to several factors. These include competing mortality from o...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.131980

    authors: Genik PC,Bielefeldt-Ohmann H,Liu X,Story MD,Ding L,Bush JM,Fallgren CM,Weil MM

    更新日期:2014-02-01 00:00:00

  • Genes and proteins differentially expressed during in vitro malignant transformation of bovine pancreatic duct cells.

    abstract::Pancreatic carcinoma has an extremely bad prognosis due to lack of early diagnostic markers and lack of effective therapeutic strategies. Recently, we have established an in vitro model recapitulating the first steps in the carcinogenesis of the pancreas. SV40 large T antigen-immortalized bovine pancreatic duct cells ...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.06754

    authors: Jesnowski R,Zubakov D,Faissner R,Ringel J,Hoheisel JD,Lösel R,Schnölzer M,Löhr M

    更新日期:2007-02-01 00:00:00

  • Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells.

    abstract::Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whet...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2015.09.003

    authors: Mukherjee A,Ma Y,Yuan F,Gong Y,Fang Z,Mohamed EM,Berrios E,Shao H,Fang X

    更新日期:2015-09-01 00:00:00

  • Pushing the optical imaging limits of cancer with multi-frequency-band raster-scan optoacoustic mesoscopy (RSOM).

    abstract::Angiogenesis is a central cancer hallmark, necessary for supporting tumor growth and metastasis. In vivo imaging of angiogenesis is commonly applied, to understand dynamic processes in cancer development and treatment strategies. However, most radiological modalities today assess angiogenesis based on indirect mechani...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1016/j.neo.2014.12.010

    authors: Omar M,Schwarz M,Soliman D,Symvoulidis P,Ntziachristos V

    更新日期:2015-02-01 00:00:00

  • CCN6 knockdown disrupts acinar organization of breast cells in three-dimensional cultures through up-regulation of type III TGF-β receptor.

    abstract::While normal cells in the human breast are organized into acinar structures, disruption of the acinar architecture is a hallmark of cancer. In a three-dimensional model of morphogenesis, we show that down-regulation of the matrix-associated tumor suppressor protein CCN6 (WNT1-inducible-signaling pathway protein 3) dis...

    journal_title:Neoplasia (New York, N.Y.)

    pub_type: 杂志文章

    doi:10.1593/neo.121322

    authors: Pal A,Huang W,Toy KA,Kleer CG

    更新日期:2012-11-01 00:00:00