Expression of transforming growth factor alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met and acidic fibroblast growth factor/fibroblast growth factor receptors during hepatocarcinogenesis.


:It is widely believed that abnormal production of polypeptide growth factors, together with other molecular alterations, play an important role in neoplastic development. Transforming growth factor alpha (TGFalpha), hepatocyte growth factor (HGF) and acidic fibroblast growth factor (aFGF) are the three major growth factors that contribute to liver regeneration occurring via both hepatocyte replication and oval cell proliferation. It is not clear, however, whether and to what extent these growth factors are also involved in hepatocarcinogenesis. In the present study, the gene expression of TGFalpha, HGF and aFGF and their corresponding receptors was examined by Northern blotting and in situ hybridization during hepatocarcinogenesis induced by the Solt-Farber protocol. All three growth factor/receptor systems, TGFalpha/epidermal growth factor receptor (EGFR), HGF/c-met and aFGF/FGF receptors (flg and bek) were significantly elevated at early time points when oval cells were proliferating. Their respective expression decreased after 1 month and remained at a low level until the development of liver tumors. In all hepatocellular carcinomas (HCC) examined, the transcripts of TGFalpha and aFGF were highly expressed, while those of HGF were low. With regard to the receptor expression in the tumors, EGFR was present at varying levels, c-met was expressed at higher levels and flg increased significantly, whereas bek remained at low levels. These data suggest that TGFalpha and aFGF are the major growth factors involved in the progression of HCC, and that the signal of aFGF is mainly transduced by the receptor flg in HCC. Furthermore, HCC cells were phenotypically very similar to oval cells with regard to the gene expression of growth factor/receptor systems. These results, along with the finding that all the HCC cells are positive for the oval cell antigen OV6, and that cytokeratin 19 is heavily expressed in both tumor and oval cells, strongly suggest that at least some of the HCC induced by the Solt-Farber protocol may be derived from oval cells.






Hu Z,Evarts RP,Fujio K,Omori N,Omori M,Marsden ER,Thorgeirsson SS




Has Abstract


1996-05-01 00:00:00












  • hMSH3 overexpression and cellular response to cytotoxic anticancer agents.

    abstract::Mutations or transcriptional silencing of mismatch repair genes have been linked with tumour cell resistance to O(6)-guanine methylating agents, 6-thioguanine, cisplatin, doxorubicin and etoposide. Recently, it has been demonstrated that overexpression of the MSH3 protein is associated with depletion of the mismatch b...


    pub_type: 杂志文章


    authors: Pepponi R,Graziani G,Falcinelli S,Vernole P,Levati L,Lacal PM,Pagani E,Bonmassar E,Jiricny J,D'Atri S

    更新日期:2001-08-01 00:00:00

  • A variant in the CHEK2 promoter at a methylation site relieves transcriptional repression and confers reduced risk of lung cancer.

    abstract::Checkpoint kinase (CHEK) 2, a tumor suppressor gene, plays an essential role in the DNA damage checkpoint response cascade. We first investigated two polymorphisms in the proximal promoter of the CHEK2 gene and evaluated their associations with the risk of lung cancer in a case-control study using 500 incident lung ca...


    pub_type: 杂志文章


    authors: Zhang S,Lu J,Zhao X,Wu W,Wang H,Lu J,Wu Q,Chen X,Fan W,Chen H,Wang F,Hu Z,Jin L,Wei Q,Shen H,Huang W,Lu D

    更新日期:2010-07-01 00:00:00

  • Genome-wide analysis identifies a tumor suppressor role for aminoacylase 1 in iron-induced rat renal cell carcinoma.

    abstract::A growing number of studies indicate a link between oxidative stress and cancer. We previously developed a rat model of renal cell carcinoma (RCC) induced by ferric nitrilotriacetate (Fe-NTA). Here, we performed a genome-wide analysis to study characteristics of genomic alteration and identify putative genes involved ...


    pub_type: 杂志文章


    authors: Zhong Y,Onuki J,Yamasaki T,Ogawa O,Akatsuka S,Toyokuni S

    更新日期:2009-01-01 00:00:00

  • 8-Hydroxyguanine (7,8-dihydro-8-oxoguanine) in hot spots of the c-Ha-ras gene: effects of sequence contexts on mutation spectra.

    abstract::We previously reported that 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) at the second position of codon 12 of the c-Ha-ras gene induces many types of mutations in NIH3T3 cells. In this study we incorporated the modified base into the first and second positions of codon 12 in the coding strand and into the first positi...


    pub_type: 杂志文章


    authors: Kamiya H,Murata-Kamiya N,Koizume S,Inoue H,Nishimura S,Ohtsuka E

    更新日期:1995-04-01 00:00:00

  • U.v.-induced DNA damage and its repair in human skin in vivo studied by sensitive immunohistochemical methods.

    abstract::Antibodies specific for u.v.-induced DNA damage were raised in rabbits, and used to study damage and repair of nuclear DNA in nude mouse and human skin in vivo by immuno-fluorescence and immunoperoxidase techniques. Purification of the antibodies by affinity chromatography strongly reduced unspecific background staini...


    pub_type: 杂志文章


    authors: Eggset G,Volden G,Krokan H

    更新日期:1983-01-01 00:00:00

  • Synergistic induction of DNA strand breakage by cigarette tar and nitric oxide.

    abstract::Cigarette smoking is a major cause of human cancer at a variety of sites, although its carcinogenic mechanisms remains unestablished. Cigarette smoke can be divided into two phases, gas phase and particulate matter (tar). Both phases contain high concentrations of oxidants and free radicals, especially nitric oxide (N...


    pub_type: 杂志文章


    authors: Yoshie Y,Ohshima H

    更新日期:1997-07-01 00:00:00

  • No tumor-specific expression levels of protein kinase C isoenzymes and of c-fos in human breast cancer cell cultures.

    abstract::Epithelial cells derived from 46 human breast tissue samples of patients suffering from breast cancer have been cultivated. Twenty-five of these cell cultures stemmed from normal and 21 from tumor tissues. Moderate to large variations of protein levels of three protein kinase C (PKC) isoenzymes (alpha, delta and epsil...


    pub_type: 杂志文章


    authors: Imber R,Haberthür F,Meier F,Filipuzzi I,Almendral AC

    更新日期:1994-02-01 00:00:00

  • Comparison of arsenic-induced cell transformation, cytotoxicity, mutation and cytogenetic effects in Syrian hamster embryo cells in culture.

    abstract::Sodium arsenite and sodium arsenate were observed to induce morphological transformation of Syrian hamster embryo cells in a dose-dependent manner. A linear dose-dependence with a slope of approximately 1 was observed with both compounds when the data were plotted on a log-log graph. The trivalent sodium arsenite was ...


    pub_type: 杂志文章


    authors: Lee TC,Oshimura M,Barrett JC

    更新日期:1985-10-01 00:00:00

  • Correlation between the DNA damage in urinary bladder epithelium and the urinary 2-phenyl-1,4-benzoquinone levels from F344 rats fed sodium o-phenylphenate in the diet.

    abstract::The relationship between urinary metabolites and DNA damage in the urinary bladder epithelium of male and female rats was tested by alkaline elution assay after an intravesical injection of OPP or its urinary metabolites. 2-Phenyl-1,4-benzoquinone (PBQ) revealed a weak DNA-damaging activity in both sexes at 0.05-0.1%....


    pub_type: 杂志文章


    authors: Morimoto K,Sato M,Fukuoka M,Hasegawa R,Takahashi T,Tsuchiya T,Tanaka A,Takahashi A,Hayashi Y

    更新日期:1989-10-01 00:00:00

  • Orotic acid, a promoter of liver carcinogenesis induces DNA damage in rat liver.

    abstract::Orotic acid, a precursor of pyrimidine nucleotide biosynthesis and a promoter for liver carcinogenesis, when fed at 1% level in a diet for 5 weeks resulted in liver DNA damage. The damage can be monitored as alkali-labile lesions using alkaline sucrose gradients as well as alkaline elution technique. Furthermore, the ...


    pub_type: 杂志文章


    authors: Rao PM,Rajalakshmi S,Alam A,Sarma DS,Pala M,Parodi S

    更新日期:1985-05-01 00:00:00

  • Inhibition of protein farnesyltransferase: a possible mechanism of tumor prevention by dehydroepiandrosterone sulfate.

    abstract::Dehydroepiandrosterone sulfate (DHEAS) is the most abundant adrenal steroid with apparent anticarcinogenic properties. Given our recent observation of the dehydro-epiandrosterone-mediated inhibition of protein isoprenylation and the fact that 99% of the circulating dehydro-epiandrosterone is sulfated, with less than 1...


    pub_type: 杂志文章,收录出版


    authors: Schulz S,Nyce JW

    更新日期:1994-11-01 00:00:00

  • Bile acids do not form adducts when incubated with DNA in vitro.

    abstract::Bile acids have been implicated in the aetiology of colon cancer. We have previously found, using 32P-postlabelling, that bile from control patients and from patients with familial adenomatous polyposis (FAP) produces DNA adducts when incubated with salmon sperm DNA in vitro. In the present study we have incubated the...


    pub_type: 杂志文章


    authors: Scates DK,Spigelman AD,Venitt S

    更新日期:1994-12-01 00:00:00

  • Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols.

    abstract::We studied the modulating effects of caffeic acid and chlorogenic acid (two common coffee polyphenols) on the in vitro methylation of synthetic DNA substrates and also on the methylation status of the promoter region of a representative gene in two human cancer cells lines. Under conditions that were suitable for the ...


    pub_type: 杂志文章


    authors: Lee WJ,Zhu BT

    更新日期:2006-02-01 00:00:00

  • Acetylation of 2-aminofluorene derivatives by dog hepatic microsomes.

    abstract::Dog urinary bladder is a target organ of carcinogenic arylamines. However, dog hepatic and urothelial cytosols lack acetylation enzymes that are capable of activating N-hydroxy metabolites of arylamines, suggesting that other enzymes may be involved. In the present study, we found that dog liver microsomes were capabl...


    pub_type: 杂志文章


    authors: Sone T,Zukowski K,Land SJ,King CM,Wang CY

    更新日期:1991-10-01 00:00:00

  • Studies on the mechanism by which a tumor promoter inhibits binding of epidermal growth factor to cellular receptors.

    abstract::This study analyzes the mechanism by which the tumor promoter 12-0-tetradecanoyl-phorbol 13-acetate (TPA) inhibits binding of epidermal growth factor (EGF) to its membrane receptors in HeLa cells. Kinetic studies indicate that inhibition of EGF binding occurs within a few minutes after exposure of cells to TPA; delaye...


    pub_type: 杂志文章


    authors: Lee LS,Weinstein IB

    更新日期:1980-08-01 00:00:00

  • Can supplementation of phytoestrogens/insoluble fibers help the management of duodenal polyps in familial adenomatous polyposis?

    abstract::Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder, and prophylactic colectomy has been shown to decrease the incidence of colorectal cancer (CRC). Duodenal cancer and desmoids are now the leading causes of death in FAP. We evaluate whether 3 months of oral supplementation with a patented...


    pub_type: 临床试验,杂志文章


    authors: Calabrese C,Rizzello F,Gionchetti P,Calafiore A,Pagano N,De Fazio L,Valerii MC,Cavazza E,Strillacci A,Comelli MC,Poggioli G,Campieri M,Spisni E

    更新日期:2016-06-01 00:00:00

  • Requirement for human AP endonuclease 1 for repair of 3'-blocking damage at DNA single-strand breaks induced by reactive oxygen species.

    abstract::The major mammalian apurinic/apyrimidinic (AP) endonuclease (APE1) plays a central role in the DNA base excision repair pathway (BER) in two distinct ways. As an AP endonuclease, it initiates repair of AP sites in DNA produced either spontaneously or after removal of uracil and alkylated bases in DNA by monofunctional...


    pub_type: 杂志文章


    authors: Izumi T,Hazra TK,Boldogh I,Tomkinson AE,Park MS,Ikeda S,Mitra S

    更新日期:2000-07-01 00:00:00

  • Diacylglycerol is an effector of the clonal expansion of cells containing activated Ha-ras genes.

    abstract::Diacylglycerols (DAG) are lipid second messengers which are generated during phospholipase-catalyzed hydrolysis of phospholipids. The model DAG, sn-1,2-didecanoylglycerol (DIC10), is an effective topical tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. We now report that 11/12 of DMBA-init...


    pub_type: 杂志文章


    authors: Mills KJ,Reynolds SH,Smart RC

    更新日期:1993-12-01 00:00:00

  • DNA adducts of the ubiquitous environmental contaminant cyclopenta[cd]pyrene.

    abstract::The bioactivation of cyclopenta[cd]pyrene (CPP) was investigated to determine the major DNA adduct-forming metabolite(s) of this widespread environmental contaminant and suspect carcinogen. DNA adducts were analyzed by 32P-postlabeling. Four major and at least seven minor adducts formed when CPP was incubated with cal...


    pub_type: 杂志文章


    authors: Beach AC,Gupta RC

    更新日期:1994-05-01 00:00:00

  • Skin tumor formation in the European hamster (Cricetus cricetus L.) after topical initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA).

    abstract::Initiation with the carcinogen 7,12-dimethylbenz[a]anthracene followed by promotion with the hyperplasiogenic phorbol ester 12-O-tetradecanoylphorbol-13-acetate carried out on the dorsal skin of European hamsters (Cricetus cricetus L.) led to the formation of a broad spectrum of skin tumors in terms of a two-stage pri...


    pub_type: 杂志文章


    authors: Goerttler K,Loehrke H,Hesse B,Schweizer J

    更新日期:1984-04-01 00:00:00

  • The effect of dietary lipid on skin tumor promotion by benzoyl peroxide: comparison of fish, coconut and corn oil.

    abstract::Fish or vegetable oils were fed during the promotion stage of a mouse skin carcinogenesis model in order to investigate the effects of dietary fat on tumor development. Two weeks after initiation with 10 nmol dimethylbenz[a]anthracene, SENCAR mice were divided into five groups and maintained on one of the following se...


    pub_type: 杂志文章


    authors: Locniskar M,Belury MA,Cumberland AG,Patrick KE,Fischer SM

    更新日期:1991-06-01 00:00:00

  • Phosphorylation of topoisomerase I in L5178Y-S cells is associated with poly(ADP-ribose) metabolism.

    abstract::The reason for different phosphorylation of topoisomerase I in two sublines of L5178Y murine lymphoma (LY cells) was investigated. Camptothecin-resistant LY-S cells show increased poly(ADP-ribose) level and lowered topoisomerase I phosphorylation compared to camptothecin-sensitive LY-R cells. In this study diminished ...


    pub_type: 杂志文章


    authors: Staron K,Kowalska-Loth B,Nieznanski K,Szumiel I

    更新日期:1996-03-01 00:00:00

  • Promotion, but not progression, effects of tamoxifen on uterine carcinogenesis in mice initiated with N-ethyl-N'-nitro-N-nitrosoguanidine.

    abstract::Effects of tamoxifen (TAM) on development of uterine endometrial carcinogenesis were studied in intact and ovariectomized (OVX) mice initiated with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). In experiment I, animals were implanted with cholesterol (ChL, controls) or TAM (5% w/w) and/or 17beta-oestradiol (E(2), 0.5% w...


    pub_type: 杂志文章


    authors: Takahashi M,Shimomoto T,Miyajima K,Iizuka S,Watanabe T,Yoshida M,Kurokawa Y,Maekawa A

    更新日期:2002-09-01 00:00:00

  • Organ-specific oxidative DNA damage associated with normal birth in rats.

    abstract::Mammalian DNA contains bulky endogenous DNA modifications (I-compounds), which increase with age in unexposed animals, as shown by 32P-postlabeling. We have examined the perinatal formation of a subclass (type II) of I-compounds in rat liver, kidney, skin and lung. These I-compounds represent bulky oxidative DNA lesio...


    pub_type: 杂志文章


    authors: Randerath E,Zhou GD,Randerath K

    更新日期:1996-12-01 00:00:00

  • Transforming growth factor beta1 enhances tumor promotion in mouse skin carcinogenesis.

    abstract::Transforming growth factor beta1 (TGFbeta1) expression is elevated by tumor promoters in the mouse skin, but its role in tumor promotion has not been well defined. To investigate this, we have compared TGFbeta1+/+ and +/- mice in a two-stage skin chemical carcinogenesis protocol. Surprisingly, TGFbeta1+/- mice had few...


    pub_type: 杂志文章


    authors: Pérez-Lorenzo R,Markell LM,Hogan KA,Yuspa SH,Glick AB

    更新日期:2010-06-01 00:00:00

  • Prostaglandin E receptor EP3 deficiency modifies tumor outcome in mouse two-stage skin carcinogenesis.

    abstract::We have recently shown that the prostaglandin E(2) (PGE(2)) receptor EP(3) plays an important role in suppression of colon cancer cell proliferation and that its deficiency enhances late stage colon carcinogenesis. Here we examined the effects of EP(3)-deficiency on two-stage skin carcinogenesis. 7,12-Dimethylbenz[a]a...


    pub_type: 杂志文章


    authors: Shoji Y,Takahashi M,Takasuka N,Niho N,Kitamura T,Sato H,Maruyama T,Sugimoto Y,Narumiya S,Sugimura T,Wakabayashi K

    更新日期:2005-12-01 00:00:00

  • Increased formation of hepatic N2-ethylidene-2'-deoxyguanosine DNA adducts in aldehyde dehydrogenase 2-knockout mice treated with ethanol.

    abstract::N2-ethylidene-2'-deoxyguanosine (N2-ethylidene-dG) is a major DNA adduct induced by acetaldehyde. Although it is unstable in the nucleoside form, it is relatively stable when present in DNA. In this study, we analyzed three acetaldehyde-derived DNA adducts, N2-ethylidene-dG, N2-ethyl-2'-deoxyguanosine (N2-Et-dG) and a...


    pub_type: 杂志文章


    authors: Matsuda T,Matsumoto A,Uchida M,Kanaly RA,Misaki K,Shibutani S,Kawamoto T,Kitagawa K,Nakayama KI,Tomokuni K,Ichiba M

    更新日期:2007-11-01 00:00:00

  • Bovine bladder and liver cell and homogenate-mediated mutagenesis of Salmonella typhimurium with aromatic amines.

    abstract::Comparisons of aromatic amine activation were made by using intact cells or cell homogenates (S-9) from bovine bladder urothelium and liver. Since both liver and bladder are thought to contribute carcinogenic metabolites for bladder cancer initiation, comparisons of these two organs' relative ability to activate aroma...


    pub_type: 杂志文章


    authors: Hix C,Oglesby L,MacNair P,Sieg M,Langenbach R

    更新日期:1983-11-01 00:00:00

  • Effects of catechol on the induction of tumors in mouse skin by 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes.

    abstract::Catechol (1,2-dihydroxybenzene) is a major phenolic compound present in the co-carcinogenic fraction of cigarette tar. It has been shown to be a potent co-carcinogen with benzo[a]pyrene (BaP) in mouse skin. In this study we have examined the co-carcinogenic and co-initiating activities of catechol with racemic and ena...


    pub_type: 杂志文章


    authors: Melikian AA,Jordan KG,Braley J,Rigotty J,Meschter CL,Hecht SS,Hoffmann D

    更新日期:1989-10-01 00:00:00

  • The assessment of DNA damage and repair in rat nasal epithelial cells.

    abstract::A methodology for the isolation and culture of rat nasal turbinates was developed with the aim of studying chemically-induced genotoxic effects in the nasal epithelium. DNA damage, as assessed by alkaline elution, and unscheduled DNA synthesis, as measured by quantitative autoradiography, were observed in the cells of...


    pub_type: 杂志文章


    authors: Bermudez E,Allen PF

    更新日期:1984-11-01 00:00:00