Increased expression of and sensitivity to transforming growth factor-alpha: a promotive role during rat liver carcinogenesis.

Abstract:

:The influence of the tumor promoter 2-acetylaminofluorene (2-AAF) on cell proliferation and on the epidermal growth factor receptor (EGFR) system was assessed in normal and nodular rat livers. DNA replication in vivo was inhibited below the detection level after 8d of dietary 2-AAF treatment of previously unexposed rats. The 2-AAF-induced growth inhibition was accompanied by downregulation of the number of epidermal growth factor (EGF)-binding sites and decreased levels of EGFR transcripts, whereas no changes in the transforming growth factor-alpha (TGF-alpha) mRNA levels were observed. The persistent liver nodules generated by intermittent 2-AAF-feeding had a 30- to 35-fold higher replicating cell fraction than normal liver. Treatment with 2-AAF in vivo reduced the replicating cell fraction to one third in nodules after 14 d of 2-AAF treatment. The initial EGFR mRNA levels and number of EGF binding sites in nodules before 2-AAF administration was about 605 that of control livers and was slightly reduced by 2-AAF feeding. The levels of EGFR mRNA after 14 d of 2-AAF feeding were thus similar in the nodules and in the 2-AAF-treated control livers, whereas the fraction of proliferating cells in nodules after the 2-AAF treatment was much larger than in normal liver. The TGF-alpha mRNA level in the nodules was found to be 1.4-fold and in malignant hepatomas 1.7-fold the level in normal liver. Primary hepatocytes isolated from control livers were four to five times more sensitive to replicative stimulation with EGF than with TGF-alpha, whereas nodular cells responded at lower concentrations than control cells and equally well to both EGF and TGF-alpha. We conclude that the decreased amounts of EGFR in the nodular cells with respect to proliferative stimulation could be more than compensated for by elevated synthesis of TGF-alpha combined with an increased TGF-alpha sensitivity. Collectively, these changes implicate TGF-alpha in sustaining cell proliferation during chemically induced rat liver carcinogenesis.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Strömblad S,Eriksson LC,Andersson G

doi

10.1002/mc.2940100207

subject

Has Abstract

pub_date

1994-06-01 00:00:00

pages

97-104

issue

2

eissn

0899-1987

issn

1098-2744

journal_volume

10

pub_type

杂志文章
  • Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer.

    abstract::Obesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20764

    authors: Carroll PA,Healy L,Lysaght J,Boyle T,Reynolds JV,Kennedy MJ,Pidgeon G,Connolly EM

    更新日期:2011-08-01 00:00:00

  • Aberrant transforming growth factor-beta signaling in azoxymethane-induced mouse colon tumors.

    abstract::Alterations in the transforming growth factor-beta (TGF-beta) pathway are implicated in the pathogenesis of colorectal cancer. We hypothesize that alterations in the TGF-beta pathway contribute to differential sensitivity of mice to the colon carcinogen azoxymethane (AOM). A/J (sensitive) and AKR/J (resistant) mice we...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.1055

    authors: Guda K,Giardina C,Nambiar P,Cui H,Rosenberg DW

    更新日期:2001-08-01 00:00:00

  • Identification of a liver cirrhosis signature in plasma for predicting hepatocellular carcinoma risk in a population-based cohort of hepatitis B carriers.

    abstract::Liver cirrhosis is a critical state in the natural course of hepatocellular carcinoma (HCC). We sought to investigate the potential of in-depth proteomics to reveal plasma protein signatures that reflect common networks/pathways of liver cirrhosis, and to determine whether the cirrhosis-related signature in plasma is ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21952

    authors: Liu CC,Wang YH,Chuang EY,Tsai MH,Chuang YH,Lin CL,Liu CJ,Hsiao BY,Lin SM,Liu LY,Yu MW

    更新日期:2014-01-01 00:00:00

  • Differences in ornithine decarboxylase and androgen receptor allele frequencies among ethnic groups.

    abstract::Recent evidence suggests that the A allele of the ornithine decarboxylase (ODC) gene is a genetic risk factor for prostate cancer. ODC is a target gene of the highly polymorphic androgen receptor (AR) gene, short alleles of which have been associated in some studies with increased prostate cancer risk. We determined O...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20047

    authors: O'Brien TG,Guo Y,Visvanathan K,Sciulli J,McLaine M,Helzlsouer KJ,Watkins-Bruner D

    更新日期:2004-10-01 00:00:00

  • Deciphering the biochemical and molecular mechanism underlying the in vitro and in vivo chemotherapeutic efficacy of ruthenium quercetin complex in colon cancer.

    abstract::Flavonoids are the most investigated phytochemicals due to their pharmacological and therapeutic activities. Their ability to chelate with metal ions has resulted in the emergence of a new category of molecules with a broader spectrum of pharmacological activities. In this study, the ruthenium quercetin complex has be...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22792

    authors: Roy S,Das R,Ghosh B,Chakraborty T

    更新日期:2018-06-01 00:00:00

  • Overexpression of Evi-1 oncoprotein represses TGF-β signaling in colorectal cancer.

    abstract::Human colorectal cancer (CRC) cells are resistant to the anti-proliferative effect of transforming growth factor-β (TGF-β), suggesting that disruption of TGF-β signaling plays an important role in colorectal carcinogenesis. Ecotropic virus integration site-1 (Evi-1) oncoprotein represses TGF-β signaling by interacting...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21852

    authors: Deng X,Cao Y,Liu Y,Li F,Sambandam K,Rajaraman S,Perkins AS,Fields AP,Hellmich MR,Townsend CM Jr,Thompson EA,Ko TC

    更新日期:2013-04-01 00:00:00

  • Identification of chromatin-accessible domains in non-alcoholic steatohepatitis-derived hepatocellular carcinoma.

    abstract::Non-alcoholic steatohepatitis (NASH) is becoming one of the major causes of hepatocellular carcinoma (HCC) in the United States and Western countries; however, the molecular mechanisms associated with NASH-related liver carcinogenesis are not well understood. In the present study, we investigated cancer-associated chr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22818

    authors: Dechassa ML,Tryndyak V,de Conti A,Xiao W,Beland FA,Pogribny IP

    更新日期:2018-08-01 00:00:00

  • Gene expression profiling as a tool for basic analysis and clinical application of human cancer.

    abstract::The sequentiation of the human genome, together with the development of high throughput technologies, particularly gene-expression profiling, is giving us the opportunity to describe biological features in a quantitative manner. Here we review the use of global gene expression analyses in cancer research. Microarray a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20430

    authors: García-Escudero R,Paramio JM

    更新日期:2008-08-01 00:00:00

  • An in vitro system to characterize prostate cancer progression identified signaling required for self-renewal.

    abstract::Mutations in RB and PTEN are linked to castration resistance and poor prognosis in prostate cancer. Identification of genes that are regulated by these tumor suppressors in a context that recapitulates cancer progression may be beneficial for discovering novel therapeutic targets. Although various genetically engineer...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22444

    authors: Salah M,Nishimoto Y,Kohno S,Kondoh A,Kitajima S,Muranaka H,Nishiuchi T,Ibrahim A,Yoshida A,Takahashi C

    更新日期:2016-12-01 00:00:00

  • Codon 61 mutations in the c-Harvey-ras gene in mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene plus okadaic acid class tumor promoters.

    abstract::Three okadaic acid class tumor promoters, okadaic acid, dinophysistoxin-1, and calyculin A, have potent tumor-promoting activity in two-stage carcinogenesis experiments on mouse skin. DNA isolated from tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and each of these tumor promoters revealed the same mutation ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940020403

    authors: Fujiki H,Suganuma M,Yoshizawa S,Kanazawa H,Sugimura T,Manam S,Kahn SM,Jiang W,Hoshina S,Weinstein IB

    更新日期:1989-01-01 00:00:00

  • Human cDNA-expressed cytochrome P450 IA2: mutagen activation and substrate specificity.

    abstract::The vaccinia virus cDNA expression system was used to produce human cytochrome P450 IA2 in a hepatoma cell line that is devoid of significant basal levels of P450. The expressed enzyme yielded a reduced carbon monoxide-bound difference spectrum with a lambda max of 449 nm. Catalytic activities and mutagen activation a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940020405

    authors: Aoyama T,Gonzalez FJ,Gelboin HV

    更新日期:1989-01-01 00:00:00

  • Differential susceptibility to carcinogen-induced amplification of SV40 and dhfr sequences in SV40-transformed human keratinocytes.

    abstract::Gene amplification contributes to carcinogenesis by enhancing proto-oncogene activity and causing chromosomal instability. The ease of detecting amplified tumor-virus sequences has encouraged use of this system as a surrogate for studying the molecular events involved in endogenous gene amplification. We report here a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940060306

    authors: Rossman TG,Wolosin D

    更新日期:1992-01-01 00:00:00

  • MAPK pathways regulation by DUSP1 in the development of osteosarcoma: Potential markers and therapeutic targets.

    abstract::Osteosarcoma (OS) is the most frequent primary bone tumor that affect children and adolescents. This tumor is highly aggressive with high risk of metastasis and the implementation of new drugs has not been successful. The search for biomarkers or new therapeutic targets is urgently needed and can help in advances of O...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22619

    authors: Lopes LJS,Tesser-Gamba F,Petrilli AS,de Seixas Alves MT,Garcia-Filho RJ,Toledo SRC

    更新日期:2017-06-01 00:00:00

  • bcl-2 delay of alkylating agent-induced apoptotic death in a murine hemopoietic stem cell line.

    abstract::Many cytotoxic agents kill cells by invoking a specific death pathway termed physiological cell death, or apoptosis. Treatment of a murine hemopoietic stem cell line, FDCP-mix, with methylmethanesulfonate (MMS) or N'-methyl-N'-nitrosourea (MNU) leads to death by apoptosis. Retroviral gene transfer was used to overexpr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940110109

    authors: Fairbairn LJ,Cowling GJ,Dexter TM,Rafferty JA,Margison GP,Reipert B

    更新日期:1994-09-01 00:00:00

  • Centchroman altered the expressions of tumor-related genes through active chromatin modifications in mammary cancer.

    abstract::Centchroman (CC), a female oral contraceptive, has been shown to possess breast anti-cancer activities. Recently, we have shown CC-mediated antimetastatic effect through reversal of epithelial-to-mesenchymal transition (EMT) in breast cancer. The loss of tumor suppressor genes (TSGs) has been shown to promote EMT in b...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22424

    authors: Khan S,Shukla S,Sinha S,Meeran SM

    更新日期:2016-11-01 00:00:00

  • Phase II enzyme inducer, sulforaphane, inhibits UVB-induced AP-1 activation in human keratinocytes by a novel mechanism.

    abstract::Ultraviolet (UV) light-induced activation of activator protein-1 (AP-1), resulting at least in part from oxidative stress, promotes skin carcinogenesis. It has not yet been determined whether elevating cellular phase II enzymes and glutathione (GSH) levels inhibits the AP-1 activation. We have, therefore, examined the...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20052

    authors: Zhu M,Zhang Y,Cooper S,Sikorski E,Rohwer J,Bowden GT

    更新日期:2004-11-01 00:00:00

  • Black currant phytoconstituents exert chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis by suppression of the inflammatory response.

    abstract::Black currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti-inflammatory properties. We have previously reported that anthocyanin-rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats although the underlying me...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21860

    authors: Bishayee A,Thoppil RJ,Mandal A,Darvesh AS,Ohanyan V,Meszaros JG,Háznagy-Radnai E,Hohmann J,Bhatia D

    更新日期:2013-04-01 00:00:00

  • Reduced expression of the Rassf1a gene and its aberrant DNA methylation in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters.

    abstract::Alterations of the Rassf1a gene were investigated in pancreatic duct adenocarcinomas (PDAs) induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters. Female Syrian golden hamsters received 70 mg/kg BOP, followed by repeated exposures to an augmentation pressure regimen consisting of a choline-deficient diet combine...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20250

    authors: Shimizu K,Itsuzaki Y,Fujii H,Honoki K,Tsujiuchi T

    更新日期:2008-02-01 00:00:00

  • Constitutive and phorbol-myristate-acetate regulated antioxidant defense of mouse epidermal JB6 cells.

    abstract::Because oxidative processes can participate in tumor promotion, it is likely that the cellular antioxidant defense also plays a role. We have compared the levels of the three major antioxidant enzymes, Cu,Zn-superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), in promotable mouse epidermal JB6 cells ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940020306

    authors: Crawford DR,Amstad PA,Foo DD,Cerutti PA

    更新日期:1989-01-01 00:00:00

  • SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/β-catenin signaling.

    abstract::Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell ca...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23246

    authors: Chen L,Xie Y,Ma X,Zhang Y,Li X,Zhang F,Gao Y,Fan Y,Gu L,Wang L,Zhang X,Fu B

    更新日期:2020-10-01 00:00:00

  • Phenotypic characteristics of mouse lung adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

    abstract::The expression profile of adenoma induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice was compared with that of normal lung tissue by suppression subtractive hybridization (SSH). The mRNAs of surfactant-associated protein A (SP-A) and lysozyme showed characteristically higher transcription in t...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20070

    authors: Okubo C,Morishita Y,Minami Y,Ishiyama T,Kano J,Iijima T,Noguchi M

    更新日期:2005-02-01 00:00:00

  • Isosilybin A induces apoptosis in human prostate cancer cells via targeting Akt, NF-κB, and androgen receptor signaling.

    abstract::Prostate cancer (PCA) is the second most malignancy in American men. Advanced stage PCA cells possess unlimited replication potential as well as resistance to apoptosis. Therefore, targeting survival mechanisms and activating apoptotic machinery in PCA cells using nontoxic phytochemicals is suggested as an attractive ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20670

    authors: Deep G,Gangar SC,Oberlies NH,Kroll DJ,Agarwal R

    更新日期:2010-10-01 00:00:00

  • Induction of the mesenchymal to epithelial transition by demethylation- activated microRNA-200c is involved in the anti-migration/invasion effects of arsenic trioxide on human breast cancer cells.

    abstract::Breast cancer is a major health problem worldwide. Current standard practices for treatment of breast cancer are less than satisfactory because of high rates of metastasis. Arsenic trioxide (As(2)O(3)), which induces demethylation of DNA and causes apoptosis, has been used as an anti-tumor agent. Little is known, howe...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22157

    authors: Si L,Jiang F,Li Y,Ye X,Mu J,Wang X,Ning S,Hu C,Li Z

    更新日期:2015-09-01 00:00:00

  • The role of transforming growth factor-beta in immune suppression and chronic inflammation of squamous cell carcinomas.

    abstract::Despite a decline in the incidence of squamous cell carcinomas (SCCs) over the past 20 years, their survival rate has remained nearly the same, indicating that treatment options have not improved relative to other cancer types. Immunotherapies have a high potential for a sustained effect in SCC patients, but their res...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.23196

    authors: Strait AA,Wang XJ

    更新日期:2020-07-01 00:00:00

  • Hepatic expression of acute-phase protein genes during carcinogenesis induced by peroxisome proliferators.

    abstract::Concern exists regarding peroxisome proliferator (PP) xenobiotic exposure because many PPs are potent hepatocarcinogens in rodents. The mechanism of carcinogenicity induced by PPs is atypical compared with those of other hepatocarcinogens in that the former appears to involve alterations in expression of PP-activated ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199912)26:4<226::aid-mc2>3

    authors: Anderson SP,Cattley RC,Corton JC

    更新日期:1999-12-01 00:00:00

  • Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor growth in a mouse model of postmenopausal claudin-low breast cancer.

    abstract::Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associate...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22763

    authors: Rossi EL,Khatib SA,Doerstling SS,Bowers LW,Pruski M,Ford NA,Glickman RD,Niu M,Yang P,Cui Z,DiGiovanni J,Hursting SD

    更新日期:2018-03-01 00:00:00

  • Molecular and immune targets for Merkel cell carcinoma therapy and prevention.

    abstract::Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin, for which the exact mechanisms of carcinogenesis remain unknown. Therapeutic options for this highly aggressive malignancy have historically been limited in both their initial response and response durability. Recent improvements in our unders...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.23042

    authors: Cohen L,Tsai KY

    更新日期:2019-09-01 00:00:00

  • Anti-EGFR monoclonal antibodies enhance sensitivity to DNA-damaging agents in BRCA1-mutated and PTEN-wild-type triple-negative breast cancer cells.

    abstract::Increased epidermal growth factor receptor (EGFR) expression in triple-negative breast cancer (TNBC) is recognized as a promising therapeutic target, specifically through the use of selective EGFR inhibitors combined with chemotherapies. TNBC is characterized by genetic instability that leads to increased sensitivity ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22596

    authors: El Guerrab A,Bamdad M,Bignon YJ,Penault-Llorca F,Aubel C

    更新日期:2017-05-01 00:00:00

  • In vitro studies of steroid hormones in neurofibromatosis 1 tumors and Schwann cells.

    abstract::The most common NF1 feature is the benign neurofibroma, which consists predominantly of Schwann cells. Dermal neurofibromas usually arise during puberty and increase in number throughout adulthood. Plexiform neurofibromas, associated with larger nerves, are often congenital and can be life threatening. Malignant perip...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20236

    authors: Fishbein L,Zhang X,Fisher LB,Li H,Campbell-Thompson M,Yachnis A,Rubenstein A,Muir D,Wallace MR

    更新日期:2007-07-01 00:00:00

  • Loss of heterozygosity at 13q14 correlates with RB1 gene underexpression in human breast cancer.

    abstract::Loss of heterozygosity (LOH) on the long arm of chromosome 13 is common in human breast tumors, pointing to the existence of several suppressor genes in this region. LOH at 13q14 has been implicated in alterations of retinoblastoma gene (RB1) expression. However, attempts to identify a link between the absence of reti...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:

    authors: Bièche I,Lidereau R

    更新日期:2000-11-01 00:00:00