Activation of beta-catenin during hepatocarcinogenesis in transgenic mouse models: relationship to phenotype and tumor grade.

Abstract:

:Mutations affecting phosphorylation sites in the beta-catenin gene have been implicated in the development of human and rodent hepatocellular carcinomas (HCCs). To further investigate the involvement of this gene in hepatocarcinogenesis, we used several transgenic mouse models of hepatic tumors induced by overexpression of c-myc in the liver either alone or in combination with transforming growth factor (TGF) alpha or TGF-beta1. Activation of beta-catenin, as judged by the presence of mutations and/or nuclear translocation of the protein, was most frequent in liver tumors from c-myc (4/17; 23.5%) and c-myc/TGF-beta1 (6/18; 33.3%) transgenic mice. However, it was very rare in faster growing and histologically more aggressive HCCs developed in c-myc/TGF-alpha mice (1/20; 5%). Administration of diethylnitrosamine, phenobarbital, or 2-amino-3,8-diethylimidazo[4,5-f]quinoxaline did not significantly affect the occurrence of beta-catenin mutations. Notably, nuclear accumulation of beta-catenin was observed only in adenomas and highly differentiated carcinomas with eosinophilic phenotype. Furthermore, preneoplastic lesions with eosinophilic phenotype frequently displayed focal nuclear positivity, colocalized with areas of high proliferation. In contrast, basophilic and clear-cell foci, as well as pseudo-glandular and poorly differentiated HCCs, exhibited a normal or reduced membranous immunoreactivity for beta-catenin. These studies suggest that nuclear translocation of beta-catenin and activation of Wingless/Wnt signaling may represent an early event in liver carcinogenesis, providing a growth advantage in a subset of hepatic tumors with a more differentiated phenotype.

journal_name

Cancer Res

journal_title

Cancer research

authors

Calvisi DF,Factor VM,Loi R,Thorgeirsson SS

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

2085-91

issue

5

eissn

0008-5472

issn

1538-7445

journal_volume

61

pub_type

杂志文章
  • CD99 engagement: an effective therapeutic strategy for Ewing tumors.

    abstract::CD99 is a Mr 32,000 transmembrane molecule that shows a high level of expression on cells of the hemopoietic system as well as on Ewing tumor cells. Within the hematopoietic system, CD99 has been implicated in cell adhesion and cell death, participating in this way in the differentiation of T-cell precursors. In this ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Scotlandi K,Baldini N,Cerisano V,Manara MC,Benini S,Serra M,Lollini PL,Nanni P,Nicoletti G,Bernard G,Bernard A,Picci P

    更新日期:2000-09-15 00:00:00

  • The combination of gamma-interferon and tumor necrosis factor causes a rapid and extensive differentiation of human neuroblastoma cells.

    abstract::Neuroblastoma (NB), a tumor originating from the sympathetic nervous system, is the most common extracranial neurological tumor of childhood. Human NB cells may differentiate in vitro under treatment with biological agents, as gamma-interferon (IFN-gamma) and tumor necrosis factor (TNF). Unfortunately, NB cell lines r...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ponzoni M,Casalaro A,Lanciotti M,Montaldo PG,Cornaglia-Ferraris P

    更新日期:1992-02-15 00:00:00

  • Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes.

    abstract::Epstein-Barr virus (EBV) is associated with Burkitt lymphoma, nasopharyngeal carcinoma, opportunistic lymphomas in immunocompromised hosts, and a fraction of gastric cancers. Aberrant promoter methylation accompanies human gastric carcinogenesis, though the contribution of EBV to such somatic methylation changes has n...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-11-1349

    authors: Matsusaka K,Kaneda A,Nagae G,Ushiku T,Kikuchi Y,Hino R,Uozaki H,Seto Y,Takada K,Aburatani H,Fukayama M

    更新日期:2011-12-01 00:00:00

  • Mevalonate Pathway Provides Ubiquinone to Maintain Pyrimidine Synthesis and Survival in p53-Deficient Cancer Cells Exposed to Metabolic Stress.

    abstract::Oncogene activation and loss of tumor suppressor function changes the metabolic activity of cancer cells to drive unrestricted proliferation. Moreover, cancer cells adapt their metabolism to sustain growth and survival when access to oxygen and nutrients is restricted, such as in poorly vascularized tumor areas. We sh...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-0650

    authors: Kaymak I,Maier CR,Schmitz W,Campbell AD,Dankworth B,Ade CP,Walz S,Paauwe M,Kalogirou C,Marouf H,Rosenfeldt MT,Gay DM,McGregor GH,Sansom OJ,Schulze A

    更新日期:2020-01-15 00:00:00

  • Cytokinetic and biochemical effects of 5-iminodaunorubicin in human colon carcinoma in culture.

    abstract::The semisynthetic anthracycline, 5-iminodaunorubicin (IM), was investigated to see whether modification of the benzoquinone moiety to produce a drug with low free radical potential would alter the cytotoxic and biochemical characteristics of this drug in comparison to Adriamycin (ADR), an agent with high free radical ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Glazer RI,Hartman KD,Richardson CL

    更新日期:1982-01-01 00:00:00

  • Pathology, Chemoprevention, and Preclinical Models for Target Validation in Barrett Esophagus.

    abstract::Despite esophageal adenocarcinoma (EAC) being the most widespread among gastrointestinal cancers, with an 11-fold increase in the risk of cancer for patients with Barrett esophagus (BE), its prognosis is still poor. There is a critical need to better perceive the biology of cancer progression and identification of spe...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-18-0206

    authors: Urbanska AM,Ponnazhagan S,Mozafari M

    更新日期:2018-07-15 00:00:00

  • Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL.

    abstract::HER2-directed therapies, such as trastuzumab and lapatinib, are important treatments for breast cancer. However, some tumors do not respond or develop resistance to these agents. We isolated and characterized multiple lapatinib-resistant, HER2-positive, estrogen receptor (ER)-positive breast cancer clones derived from...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-4490

    authors: Liu L,Greger J,Shi H,Liu Y,Greshock J,Annan R,Halsey W,Sathe GM,Martin AM,Gilmer TM

    更新日期:2009-09-01 00:00:00

  • A new member of the proprotein convertase gene family (LPC) is located at a chromosome translocation breakpoint in lymphomas.

    abstract::A new member of the proprotein convertase gene family (LPC) has been identified at a chromosome translocation breakpoint occurring in a high grade lymphoma. The translocation t(11;14)(q23;q32) has been molecularly cloned and shown to be the result of a fusion between an intron in the 3' -untranslated region of LPC wit...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Meerabux J,Yaspo ML,Roebroek AJ,Van de Ven WJ,Lister TA,Young BD

    更新日期:1996-02-01 00:00:00

  • Modulation of oncogenic transcription and alternative splicing by beta-catenin and an RNA aptamer in colon cancer cells.

    abstract::Activated beta-catenin regulates the transcription of oncogenic target genes and is critical for tumorigenesis. Because nuclear functions are frequently coupled, we investigated whether it also has a role in alternative splicing of oncogenic genes. We showed that stabilized beta-catenin caused alternative splicing of ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-2526

    authors: Lee HK,Choi YS,Park YA,Jeong S

    更新日期:2006-11-01 00:00:00

  • The potential role of systemic buffers in reducing intratumoral extracellular pH and acid-mediated invasion.

    abstract::A number of studies have shown that the extracellular pH (pHe) in cancers is typically lower than that in normal tissue and that an acidic pHe promotes invasive tumor growth in primary and metastatic cancers. Here, we investigate the hypothesis that increased systemic concentrations of pH buffers reduce intratumoral a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-2394

    authors: Silva AS,Yunes JA,Gillies RJ,Gatenby RA

    更新日期:2009-03-15 00:00:00

  • Deoxycytidine Release from Pancreatic Stellate Cells Promotes Gemcitabine Resistance.

    abstract::Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States. The deoxynucleoside analogue gemcitabine is among the most effective therapies to treat PDAC, however, nearly all patients treated with gemcitabine either fail to respond or rapidly develop resistance. One hallmark of PDA...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-0960

    authors: Dalin S,Sullivan MR,Lau AN,Grauman-Boss B,Mueller HS,Kreidl E,Fenoglio S,Luengo A,Lees JA,Vander Heiden MG,Lauffenburger DA,Hemann MT

    更新日期:2019-11-15 00:00:00

  • Anti-CD20 Therapy Acts via FcγRIIIA to Diminish Responsiveness of Human Natural Killer Cells.

    abstract::Natural killer (NK) immune cells mediate antibody-dependent cellular cytotoxicity (ADCC) by aggregating FcγRIIIA/CD16, contributing significantly to the therapeutic effect of CD20 monoclonal antibodies (mAb). In this study, we show that CD16 ligation on primary human NK cells by the anti-CD20 mAb rituximab or ofatumum...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-0781

    authors: Capuano C,Romanelli M,Pighi C,Cimino G,Rago A,Molfetta R,Paolini R,Santoni A,Galandrini R

    更新日期:2015-10-01 00:00:00

  • Identification of an inactivating cysteine switch in protein kinase Cepsilon, a rational target for the design of protein kinase Cepsilon-inhibitory cancer therapeutics.

    abstract::Critical roles played by some protein kinases in neoplastic transformation and progression provide a rationale for developing selective, small-molecule kinase inhibitors as antineoplastic drugs. Protein kinase Cepsilon (PKCepsilon) is a rational target for cancer therapy, because it is oncogenic and prometastatic in t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-1989

    authors: Chu F,Koomen JM,Kobayashi R,O'Brian CA

    更新日期:2005-11-15 00:00:00

  • Amplified and overexpressed epidermal growth factor receptor gene in uncultured primary human breast carcinoma.

    abstract::We analyzed the epidermal growth factor receptor gene using a complementary DNA probe of the epidermal growth factor receptor gene in 21 uncultured primary breast carcinomas and found that the gene was amplified in three of these tumors. We further demonstrated by immunohistochemistry using a monoclonal antibody to th...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ro J,North SM,Gallick GE,Hortobagyi GN,Gutterman JU,Blick M

    更新日期:1988-01-01 00:00:00

  • Bicarbonate increases tumor pH and inhibits spontaneous metastases.

    abstract::The external pH of solid tumors is acidic as a consequence of increased metabolism of glucose and poor perfusion. Acid pH has been shown to stimulate tumor cell invasion and metastasis in vitro and in cells before tail vein injection in vivo. The present study investigates whether inhibition of this tumor acidity will...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-5575

    authors: Robey IF,Baggett BK,Kirkpatrick ND,Roe DJ,Dosescu J,Sloane BF,Hashim AI,Morse DL,Raghunand N,Gatenby RA,Gillies RJ

    更新日期:2009-03-15 00:00:00

  • A clinical evaluation of serum C3DP levels in individuals with malignant diseases.

    abstract::A human serum DNA-binding protein (C3DP) derived from complement component C3 has been found in elevated concentrations in the sera of individuals with malignant diseases. An assay system has been devised which reveals quantitative values of serum C3DP levels. Results obtained using this system indicate that normal hu...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Parsons RG,Longmire RL,Hoch SO,Hoch JA

    更新日期:1977-03-01 00:00:00

  • Expression of the O6-methylguanine-DNA methyltransferase gene MGMT in MER+ and MER- human tumor cells.

    abstract::DNA probes prepared from human O6-methylguanine-DNA methyltransferase complementary DNA were hybridized to mRNA isolated from human liver and fifteen human tumor cell lines proficient (Mer+) or deficient (Mer-) in transferase activity. Liver and Mer+ cells contained levels of transferase-specific mRNA that correlated ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Fornace AJ Jr,Papathanasiou MA,Hollander MC,Yarosh DB

    更新日期:1990-12-15 00:00:00

  • Altered expression of c-IAP1, survivin, and Smac contributes to chemotherapy resistance in thyroid cancer cells.

    abstract::Resistance to chemotherapy predicts an unfavorable outcome for patients with radioiodine-insensitive thyroid cancer. To investigate the mechanisms underlying this resistance, we evaluated the expression of four different inhibitor of apoptosis proteins, and their antagonist, Smac, in thyroid cancer cells that survived...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-3248

    authors: Tirrò E,Consoli ML,Massimino M,Manzella L,Frasca F,Sciacca L,Vicari L,Stassi G,Messina L,Messina A,Vigneri P

    更新日期:2006-04-15 00:00:00

  • Comparative dual label study of first and second generation antitumor-associated glycoprotein-72 monoclonal antibodies in colorectal cancer patients.

    abstract::Radiolabeled first-generation anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody (MAb), B72.3, has proven useful in detecting primary and secondary colorectal carcinoma. It has been anticipated that the development of second-generation, higher affinity, anti-TAG-72 MAbs, CC49 and CC83, would be of grea...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gallinger S,Reilly RM,Kirsh JC,Odze RD,Schmocker BJ,Hay K,Polihronis J,Damani MT,Shpitz B,Stern HS

    更新日期:1993-01-15 00:00:00

  • Protein kinase C delta involvement in mammary tumor cell metastasis.

    abstract::Metastasis requires cytoskeletal remodeling for migration, adhesion, and extravasation of metastatic cells. Although protein kinase C (PKC) is involved in tumor promotion/progression and cytoskeletal remodeling, its role in metastasis has not been defined. PKCdelta levels are increased in highly metastatic 13762NF mam...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kiley SC,Clark KJ,Goodnough M,Welch DR,Jaken S

    更新日期:1999-07-01 00:00:00

  • Induction and developmental expression of cytochrome P450IA1 messenger RNA in rat and human tissues: detection by the polymerase chain reaction.

    abstract::The expression of cytochrome P450 genes directly within target cells is an important determinant of human susceptibility to cancers, birth defects, and other chemically initiated diseases. One pivotal gene, CYP1A1, codes for an inducible cytochrome P450 isozyme (P450IA1) responsible for the bioactivation of numerous c...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Omiecinski CJ,Redlich CA,Costa P

    更新日期:1990-07-15 00:00:00

  • Biomedical Research Meets Toxicology: How In Vitro Chromosome Instability Methods Can Contribute to Carcinogenicity Prediction.

    abstract::Cancer is a major health concern and a leading cause of mortality. The reliable identification of carcinogens and understanding of carcinogenicity has become a main focus of biomedical research and regulatory toxicology. While biomedical research applies cellular in vitro methods to uncover the underlying mechanisms c...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-2822

    authors: Stolz A,Becker M,Wistorf E,Ertych N

    更新日期:2020-04-15 00:00:00

  • Human papillomavirus 16 E7 oncoprotein attenuates DNA damage checkpoint control by increasing the proteolytic turnover of claspin.

    abstract::The human papillomavirus (HPV) 16 E7 oncoprotein has been reported previously to stimulate DNA damage and to activate host cell DNA damage checkpoints. How HPV-16 E7 maintains proliferation despite activated DNA damage checkpoints is incompletely understood. Here, we provide evidence that cells expressing the HPV-16 E...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-0925

    authors: Spardy N,Covella K,Cha E,Hoskins EE,Wells SI,Duensing A,Duensing S

    更新日期:2009-09-01 00:00:00

  • Uptake and distribution of specific and control monoclonal antibodies in subcutaneous xenografts following intratumor injection.

    abstract::Nude mice bearing s.c. xenografts of the human colon adenocarcinoma HT29 were given intratumor injections of a mixture of 125I-labeled specific antibody (AUA1) and 131I-labeled control antibody (HMFG1), or with the labels reversed. After dissection at 1 and 4 h postadministration, both specific and control antibodies ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Rowlinson-Busza G,Bamias A,Krausz T,Epenetos AA

    更新日期:1991-06-15 00:00:00

  • Caspase-8: fly or die.

    abstract::Recent studies have revealed that procaspase-8 has an important function in cell adhesion and motility. Src phosphorylation controls this function by preventing the conversion of procaspase-8, which is an adhesion/migration factor, to mature caspase-8, which is an apoptosis-inducing factor. This provides a mechanism t...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-08-0952

    authors: Frisch SM

    更新日期:2008-06-15 00:00:00

  • Inhibition of hamster melanoma growth by estrogen.

    abstract::A malignant hamster melanoma cell line HM-1 derived from the heterogenous malignant hamster melanoma MM1 contains a specific, high affinity binding protein for estrogens. Partial purification of the binding protein with ammonium sulfate (40% saturation) increased mean binding content (3.1 +/- 1.2 (SD) fmol/mg protein)...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Schleicher RL,Hitselberger MH,Beattie CW

    更新日期:1987-01-15 00:00:00

  • Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma growth.

    abstract::The relevance of cysteine metabolism in cancer has gained considerable interest in recent years, largely focusing on its role in generating the antioxidant glutathione. Through metabolomic profiling using a combination of high-throughput liquid and gas chromatography-based mass spectrometry on a total of 69 patient-de...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-13-1423

    authors: Prabhu A,Sarcar B,Kahali S,Yuan Z,Johnson JJ,Adam KP,Kensicki E,Chinnaiyan P

    更新日期:2014-02-01 00:00:00

  • Metabolism and macromolecular covalent binding of [14C]-1-nitropyrene in isolated perfused and ventilated rat lungs.

    abstract::1-Nitropyrene (1-NP) originating from such sources as diesel exhaust emissions and coal combustion fly ash has been detected in the environment. 1-NP, in addition to being both a bacterial and mammalian mutagen, is carcinogenic in rats. The purpose of this study was to quantitate 1-NP metabolism and macromolecular cov...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bond JA,Mauderly JL

    更新日期:1984-09-01 00:00:00

  • Use of screening phase data to evaluate observer variation of sputum cytodiagnosis as an outcome measure in a chemoprevention trial.

    abstract::Sputum samples obtained during the screening phase of a chemoprevention trial in heavy smokers were evaluated independently by trained cytotechnologists and classified for degree of cellular atypia according to the method of Saccommano et al. (G. Saccommano et al., Cancer (Phila.), 33: 256-270, 1974). The level of agr...

    journal_title:Cancer research

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Browman GP,Arnold A,Levine MN,D'Souza T,Turner-Smith LM,Cayco R,Johnstone B,Birse R

    更新日期:1990-02-15 00:00:00

  • Tumor-Derived TGFβ Alters the Ability of Plasmacytoid Dendritic Cells to Respond to Innate Immune Signaling.

    abstract::A growing number of observations has suggested that plasmacytoid dendritic cells (pDC) play a critical role in tumor biology. In patients, infiltration of tumors by pDCs generally correlates with a poor prognosis, suggesting that pDCs may play an important role in the host-tumor relationship. Here, we analyze the infl...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-17-2719

    authors: Terra M,Oberkampf M,Fayolle C,Rosenbaum P,Guillerey C,Dadaglio G,Leclerc C

    更新日期:2018-06-01 00:00:00