Low expression of the Lsp1 gene in early mouse T-lymphomas induced by N-methyl-N-nitrosourea.


:The mouse Lsp1 gene encodes a 330 amino acid intracellular F-actin binding protein. Previously we showed that the mouse and human Lsp1 genes are expressed in normal B-cells and T-cells, including Thy1+ thymocytes and in normal macrophages and neutrophils. No or little LSP1 RNA and protein was found in a series of transformed mouse and human T-lymphoma cell lines, although normal antigen and lymphokine dependent T-cell lines expressed the Lsp1 gene. Here we show by Northern analysis that three mature antigen independent T-cell lines (CTLL-2, HT-2 and 532.10) which grow in the presence of lymphokine only, do not express LSP1 RNA, while mature resting and activated lymph node T-cells express high levels of LSP1 RNA. To determine whether the down-regulation of LSP1 expression is an early event which occurs in vivo in the tumor, rather than as a consequence of in vitro propagation of T-lymphoma cells, we analyzed LSP1 expression in primary T-lymphomas induced in AKR/J or AKR/J x BALB/cJ mice by a single intraperitoneal (i.p.) injection with 75 mg N-methyl-N-nitrosourea (MNU) per kg body-weight. Two- color Fluorescence Activated Cell Sorter (FACS) analysis showed that all tumors had an immature CD4+/CD8+ double positive (DP) phenotype. Many tumors contained a substantial population of CD4+ single positive (SP) cells. Since these cells may be infiltrating lymphocytes which can be expected to express the Lsp1 gene at a high level these tumors were not included in our analysis. Nineteen tumors were analyzed for Lsp1 gene expression and 13 contained reduced levels of LSP1 RNA, ranging from 4% to 44% of those found in age-matched normal thymus. Six tumors showed either no or only a small reduction in LSP1 RNA. These tumors had developed later than those expressing low levels of LSP1. The level of LSP1 RNA in tumors developing <110 days after injection of MNU was 19.1% +/- 5.2 (mean +/- SEM), while the level of LSP1 in later tumors was 78.4% +/- 13.0 (P = 0.004). Similar data were obtained when the expression of LSP1 protein was analyzed. These findings extend our previous data in several ways. First, they suggest a correlation between the down-regulation of LSP1 expression and abnormal regulation of growth or survival of immature and mature T-lymphocytes. Second, they show that down-regulation of the Lsp1 gene in transformed T-cells is not the result of prolonged in vitro culture, but occurs in the majority of primary tumors. Third, they show that there are two classes of T-lymphoma, which differ in their expression of LSP1 RNA and that the down-regulation of LSP1 is specifically associated with the early appearance of T-lymphoma after injection with MNU. This strongly suggests that the absence or reduced expression of LSP1 contributed to the transformation process and argues against the possibility that loss of LSP1 expression is a mere inconsequential epigenetic event.






Brennan L,Jongstra J




Has Abstract


1996-04-01 00:00:00












  • Prevention of dual promoting effects of pentachlorophenol, an environmental pollutant, on diethylnitrosamine-induced hepato- and cholangiocarcinogenesis in mice by green tea infusion.

    abstract::In order to explore a possibility that the custom of drinking green tea infusion is efficacious for reducing the carcinogenic risk of environmental exposure to pentachlorophenol (PCP), we examined the effects in a hepato- and cholangiocarcinogenesis model in mice exposed to diethylnitrosamine (DEN). In the first exper...


    pub_type: 杂志文章


    authors: Umemura T,Kai S,Hasegawa R,Kanki K,Kitamura Y,Nishikawa A,Hirose M

    更新日期:2003-06-01 00:00:00

  • Inhibitory effect of silymarin, an anti-hepatotoxic flavonoid, on 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity and mRNA in SENCAR mice.

    abstract::In recent years, considerable emphasis has been placed on identifying new cancer chemopreventive agents which could be useful for human populations. Silymarin, an anti-oxidant flavonoid isolated from artichoke, has been shown to possess significant activity against hepatotoxicity and other pharmacological and physiolo...


    pub_type: 杂志文章


    authors: Agarwal R,Katiyar SK,Lundgren DW,Mukhtar H

    更新日期:1994-06-01 00:00:00

  • Met receptor tyrosine kinase transactivation is involved in proteinase-activated receptor-2-mediated hepatocellular carcinoma cell invasion.

    abstract::The expression of proteinase-activated receptor (PAR)(2) in human hepatocellular carcinoma (HCC) was established by reverse transcription-polymerase chain reaction, confocal immunofluorescence and electron microscopy in permanent cell lines, primary HCC cell cultures and HCC tumor tissue. Stimulation of HCC cells with...


    pub_type: 杂志文章


    authors: Kaufmann R,Oettel C,Horn A,Halbhuber KJ,Eitner A,Krieg R,Katenkamp K,Henklein P,Westermann M,Böhmer FD,Ramachandran R,Saifeddine M,Hollenberg MD,Settmacher U

    更新日期:2009-09-01 00:00:00

  • Hypoxia and nickel inhibit histone demethylase JMJD1A and repress Spry2 expression in human bronchial epithelial BEAS-2B cells.

    abstract::Epigenetic silencing of tumor suppressor genes commonly occurs in human cancers via increasing DNA methylation and repressive histone modifications at gene promoters. However, little is known about how pathogenic environmental factors contribute to cancer development by affecting epigenetic regulatory mechanisms. Prev...


    pub_type: 杂志文章


    authors: Chen H,Kluz T,Zhang R,Costa M

    更新日期:2010-12-01 00:00:00

  • DNA adduct formation and removal in hepatic chromatin fractions from rats chronically fed 2-acetylaminofluorene.

    abstract::Continuous dietary administration of the hepatocarcinogen 2-acetylaminofluorene (AAF) to rats produces a gradual increase in hepatic DNA adducts until a plateau is reached after approximately 2 weeks. The rate of DNA adduct formation remains constant through 1 month of AAF feeding, while adduct removal profiles are bi...


    pub_type: 杂志文章


    authors: Poirier MC,Fullerton NF,Patterson ED,Beland FA

    更新日期:1990-08-01 00:00:00

  • Lycopene inhibits IGF-I signal transduction and growth in normal prostate epithelial cells by decreasing DHT-modulated IGF-I production in co-cultured reactive stromal cells.

    abstract::Prostate stromal and epithelial cell communication is important in prostate functioning and cancer development. Primary human stromal cells from normal prostate stromal cells (PRSC) maintain a smooth muscle phenotype, whereas those from prostate cancer (6S) display reactive and fibroblastic characteristics. Dihydrotes...


    pub_type: 杂志文章


    authors: Liu X,Allen JD,Arnold JT,Blackman MR

    更新日期:2008-04-01 00:00:00

  • Potentiating effect of benzo[a]pyrene and caffeine on Friend viral leukemogenesis.

    abstract::The effect of exposing mice to both a chemical carcinogen and leukemia virus with and without an inhibitor of DNA repair were compared. The data indicated that benzo[a]pyrene (BP) could exert a potentiating effect of Friend viral leukemogenesis in mice, which was dependent on the relative times of administration of th...


    pub_type: 杂志文章


    authors: Raikow RB,Okunewick JP,Buffo MJ,Jones DL,Brozovich BJ,Seeman PR,Koval TM

    更新日期:1981-01-01 00:00:00

  • Prevention of 20-methylcholanthrene-induced sarcoma by a mistletoe extract, Iscador.

    abstract::Iscador, an extract from the semi-parasitic plant Viscum album, was found to inhibit 20-methylcholanthrene-induced carcinogenesis in mice. Intraperitoneal administration of Iscador (1 mg/dose) twice weekly for 15 weeks could completely inhibit 20-methylcholanthrene-induced sarcoma in mice and protect these animals fro...


    pub_type: 杂志文章


    authors: Kuttan G,Menon LG,Kuttan R

    更新日期:1996-05-01 00:00:00

  • The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance.

    abstract::Chondrosarcoma is a form of malignant skeletal tumor of cartilaginous origin. The non-malignant form of the disease is termed chondroma. Correctly distinguishing between the two forms is essential for making therapeutic decisions. However, due to their similar histological appearances and the lack of a reliable diagno...


    pub_type: 杂志文章


    authors: Kumari R,Li H,Haudenschild DR,Fierro F,Carlson CS,Overn P,Gupta L,Gupta K,Nolta J,Yik JH,Di Cesare PE

    更新日期:2012-11-01 00:00:00

  • Morphologic transformation of the C3H 10T1/2 cell line is accompanied by altered expression of the p53 tumor suppressor gene.

    abstract::Wildtype 10T1/2 cells and 42 clonally derived morphologically transformed 10T1/2 cell lines were evaluated for expression of p53 mRNA and protein. Wildtype 10T1/2 cells expressed detectable levels of p53 mRNA and multiple immunologically distinct forms of the p53 protein, including both PAb240- and PAb246-reactive con...


    pub_type: 杂志文章


    authors: Coleman WB,Grisham JW,Smith GJ

    更新日期:1994-02-01 00:00:00

  • Cytochrome P450 1B1 and catechol-O-methyltransferase polymorphisms and endometrial cancer susceptibility.

    abstract::Estrogen production and metabolism play critical roles in the development and pathogenesis of endometrial carcinoma. Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) are two key enzymes in the estrogen metabolism pathway that result in the hydroxylation and conjugation of estradiol, respectively. W...


    pub_type: 杂志文章,多中心研究


    authors: McGrath M,Hankinson SE,Arbeitman L,Colditz GA,Hunter DJ,De Vivo I

    更新日期:2004-04-01 00:00:00

  • Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile acids.

    abstract::Although epidemiological evidence in humans and bile acid feeding studies in rodents implicate bile acids as tumor promoters, the role of endogenous bile acids in colon carcinogenesis remains unclear. In this study, we exploited mice deficient in the ileal apical sodium-dependent bile acid transporter (ASBT, encoded b...


    pub_type: 杂志文章


    authors: Raufman JP,Dawson PA,Rao A,Drachenberg CB,Heath J,Shang AC,Hu S,Zhan M,Polli JE,Cheng K

    更新日期:2015-10-01 00:00:00

  • Vinyl carbamate epoxide, a major strong electrophilic, mutagenic and carcinogenic metabolite of vinyl carbamate and ethyl carbamate (urethane).

    abstract::Vinyl carbamate epoxide (VCO) was found to possess strong electrophilic, mutagenic and carcinogenic activities. It reacted with water at 37 degrees C and pH 7.4 (phosphate buffer) to form glycolaldehyde and several related reducing compounds; none of these products were mutagenic for Salmonella typhimurium TA1535. Und...


    pub_type: 杂志文章


    authors: Park KK,Liem A,Stewart BC,Miller JA

    更新日期:1993-03-01 00:00:00

  • Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells.

    abstract::We investigated whether curcumin, a chemopreventive agent, inhibited chenodeoxycholate (CD)- or phorbol ester (PMA)-mediated induction of cyclooxygenase-2 (COX-2) in several gastrointestinal cell lines (SK-GT-4, SCC450, IEC-18 and HCA-7). Treatment with curcumin suppressed CD- and PMA-mediated induction of COX-2 prote...


    pub_type: 杂志文章


    authors: Zhang F,Altorki NK,Mestre JR,Subbaramaiah K,Dannenberg AJ

    更新日期:1999-03-01 00:00:00

  • Grainyhead-like 2 regulates epithelial plasticity and stemness in oral cancer cells.

    abstract::Grainyhead-like 2 (GRHL2) is one of the three mammalian homologues of Drosophila Grainyhead involved in epithelial morphogenesis. We recently showed that GRHL2 also controls normal epithelial cell proliferation and differentiation. In this study, we investigated the role of GRHL2 in oral carcinogenesis and the underly...


    pub_type: 杂志文章


    authors: Chen W,Yi JK,Shimane T,Mehrazarin S,Lin YL,Shin KH,Kim RH,Park NH,Kang MK

    更新日期:2016-05-01 00:00:00

  • High-risk HPV16E6 stimulates hADA3 degradation by enhancing its SUMOylation.

    abstract::Despite significant research, our understanding of the molecular mechanisms of Human Papilloma Virus (HPV) induced cancers remains incomplete. Majority of invasive cervical cancers are caused by high-risk HPV 16 and 18. Two potent HPV oncoproteins, E6 and E7, promote human malignancies by disrupting the activities of ...


    pub_type: 杂志文章


    authors: Chand V,John R,Jaiswal N,Johar SS,Nag A

    更新日期:2014-08-01 00:00:00

  • NF-kappaB inhibition radiosensitizes Ki-Ras-transformed cells to ionizing radiation.

    abstract::Most cancer cells show resistance to ionizing radiation (IR)-induced cell death. Recently, Ki-Ras was reported to be responsible for the increased radioresistance. We report here that inhibition of IR-induced activaton of nuclear transcription factor kappa B (NF-kappaB) but not of either Akt or MAPK kinase (MEK), incr...


    pub_type: 杂志文章


    authors: Kim BY,Kim KA,Kwon O,Kim SO,Kim MS,Kim BS,Oh WK,Kim GD,Jung M,Ahn JS

    更新日期:2005-08-01 00:00:00

  • Reaction products of styrene oxide with guanosine in aqueous media.

    abstract::Styrene oxide was reacted with guanosine in fully aqueous conditions, and the products were purified by cation exchange chromatography and h.p.l.c. The products were characterized by u.v. and mass spectra, loss of tritium from the C-8 position and dissociation properties. About 90% of the total product was identified,...


    pub_type: 杂志文章


    authors: Hemminki K,Hesso A

    更新日期:1984-05-01 00:00:00

  • Characterization of human buccal epithelial cells transfected with the simian virus 40 T-antigen gene.

    abstract::Serum-free cultures of normal human buccal epithelial cells were transfected with a plasmid containing the SV40 T-antigen (SV40T) gene. Two major lines developed that showed extended lifespans (between 30 and 40 weeks) as compared with the controls (approximately 6 weeks). Continued growth through one or two crises ge...


    pub_type: 杂志文章


    authors: Kulkarni PS,Sundqvist K,Betsholtz C,Höglund P,Wiman KG,Zhivotovsky B,Bertolero F,Liu Y,Grafström RC

    更新日期:1995-10-01 00:00:00

  • Metabolic cooperation in SK-HEP-1 human hepatoma cells following treatment with benzodiazepine tranquilizers.

    abstract::The ability of three benzodiazepine tranquilizers, diazepam, oxazepam and chlordiazepoxide chlorhydrate to block metabolic cooperation between human hepatoma cells was analysed using autoradiographical monitoring. Independent tests were performed with compound concentrations varying from 1 to 50 micrograms/ml. The res...


    pub_type: 杂志文章


    authors: Rolin-Limbosch S,Moens W,Szpirer C

    更新日期:1987-07-01 00:00:00

  • Fumonisin B1 dosimetry in relation to cancer initiation in rat liver.

    abstract::Dose response studies regarding the cancer initiating potential of fumonisin B1 (FB1) were conducted as a function of time. Feeding studies over 21 days indicated that FB1 induced a feed refusal effect in rats at dietary levels of 250, 500 and 750 mg FB1/kg diet. This effect was overcome after 14 days and the feed int...


    pub_type: 杂志文章


    authors: Gelderblom WC,Cawood ME,Snyman SD,Marasas WF

    更新日期:1994-02-01 00:00:00

  • Formation of macromolecular complexes and other effects of DNA treatment with diethyl and dimethyl sulfate: physico-chemical and electron microscopic studies.

    abstract::In vitro exposures of isolated DNA to one of the two carcinogenic and mutagenic chemicals, diethylsulfate or dimethylsulfate, induces several kinds of physicochemical and morphological alterations. These changes are detectable by a variety of independent techniques. A fraction of DNA treated briefly with either of the...


    pub_type: 杂志文章


    authors: Kubinski H,Kubinski ZO,Fiandt M,Konopa G

    更新日期:1981-01-01 00:00:00

  • Spontaneous basophilic foci of hepatocellular alteration in Fischer 344 female rats do not exclude iron.

    abstract::Iron exclusion has been used to identify foci of hepatocellular alteration (FHA) in rats exposed to known carcinogens. This study investigates whether basophilic FHA occurring spontaneously in aged female Fischer 344 rats also exclude iron. Female rats 514-544 days of age were given supplemental iron by injection for ...


    pub_type: 杂志文章


    authors: Stitzel KA,Horn PA,Ezra MF

    更新日期:1990-12-01 00:00:00

  • Ellagic acid induces transcription of the rat glutathione S-transferase-Ya gene.

    abstract::Induction of glutathione S-transferase (GST) enzymes can increase detoxification of carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis. To determine if the anticarcinogen ellagic acid induces cellular enzymes which detoxify carcinogens, we examined the effect of ellagic acid on the expression of g...


    pub_type: 杂志文章


    authors: Barch DH,Rundhaugen LM,Pillay NS

    更新日期:1995-03-01 00:00:00

  • Smad-Sp1 complexes mediate TGFbeta-induced early transcription of oncogenic Smad7 in pancreatic cancer cells.

    abstract::The transcription factor Sp1 has been implicated in cell-type-specific activation of transforming growth factor-beta (TGFbeta) target genes in normal epithelial cells as well as in aberrant gene activation by TGFbeta in epithelial tumor cells. Here, we have examined the interaction of Sp1 with components of the Smad s...


    pub_type: 杂志文章


    authors: Jungert K,Buck A,Buchholz M,Wagner M,Adler G,Gress TM,Ellenrieder V

    更新日期:2006-12-01 00:00:00

  • Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution.

    abstract:BACKGROUND:Variations in genetic mutations in pancreatic carcinoma between different geographical regions have not been studied extensively, especially in developing countries where pancreatic cancer is relatively rare. METHODS:We studied the molecular pathology of 54 pancreatic adenocarcinomas from Egyptian patients ...


    pub_type: 杂志文章


    authors: Soliman AS,Lo AC,Banerjee M,El-Ghawalby N,Khaled HM,Bayoumi S,Seifeldin IA,Abdel-Aziz A,Abbruzzese JL,Greenson JK,Hamilton SR

    更新日期:2007-08-01 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

  • The effect of the format of administration and the total dose of phenobarbital on altered hepatic foci following initiation in female rats with diethylnitrosamine.

    abstract::The effect of changing the format of administration as well as the total dose of the promoting agent phenobarbital (PB) on the development of altered hepatic foci (AHF) was determined in an initiation-promotion protocol with female rats fed the purified AIN-76 diet. Effects on the total number of AHF and the volume pe...


    pub_type: 杂志文章


    authors: Xu YD,Dragan YP,Young T,Pitot HC

    更新日期:1991-06-01 00:00:00

  • Analysis of EGFR, TGF-alpha, neu and c-myc in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mammary tumors using RT-PCR.

    abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a mutagen found in cooked meat, has been shown to induce mammary gland tumors in rats. Our laboratory recently observed that a high fat diet enhances the incidence and severity of PhIP-induced mammary gland cancer in rats. In the current study, reverse transcript...


    pub_type: 杂志文章


    authors: Davis CD,Snyderwine EG

    更新日期:1995-12-01 00:00:00

  • Inhibitory effects of 17beta-estradiol and 4-n-octylphenol on 7,12-dimethylbenz[a]anthracene-induced mammary tumor development in human c-Ha-ras proto-oncogene transgenic rats.

    abstract::Experiments were conducted to determine whether the natural estrogen and an environmental compound with estrogenic action, 4-n-octylphenol (4nOP), could modify tumor development in human c-Ha-ras proto-oncogene transgenic (Tg) rats which are highly susceptible to mammary and skin carcinogens. Female and male Tg and no...


    pub_type: 杂志文章


    authors: Han BS,Fukamachi K,Takasuka N,Ohnishi T,Maeda M,Yamasaki T,Tsuda H

    更新日期:2002-07-01 00:00:00