Transgenic insulin-like growth factor-1 stimulates activation of COX-2 signaling in mammary glands.


:Studies show that elevated insulin-like growth factor-1 (IGF-1) levels are associated with an increased risk of breast cancer; however, mechanisms through which IGF-1 promotes mammary tumorigenesis in vivo have not been fully elucidated. To assess the possible involvement of COX-2 signaling in the pro-tumorigenic effects of IGF-1 in mammary glands, we used the unique BK5.IGF-1 mouse model in which transgenic (Tg) mice have significantly increased incidence of spontaneous and DMBA-induced mammary cancer compared to wild type (WT) littermates. Studies revealed that COX-2 expression was significantly increased in Tg mammary glands and tumors, compared to age-matched WTs. Consistent with this, PGE(2) levels were also increased in Tg mammary glands. Analysis of expression of the EP receptors that mediate the effects of PGE(2) showed that among the four G-protein-coupled receptors, EP3 expression was elevated in Tg glands. Up-regulation of the COX-2/PGE(2) /EP3 pathway was accompanied by increased expression of VEGF and a striking enhancement of angiogenesis in IGF-1 Tg mammary glands. Treatment with celecoxib, a selective COX-2 inhibitor, caused a 45% reduction in mammary PGE(2) levels, attenuated the influx of mast cells and reduced vascularization in Tg glands. These findings indicate that the COX-2/PGE(2) /EP3 signaling pathway is involved in IGF-1-stimulated mammary tumorigenesis and that COX-2-selective inhibitors may be useful in the prevention or treatment of breast cancer associated with elevated IGF-1 levels in humans. © 2011 Wiley Periodicals, Inc.


Mol Carcinog


Molecular carcinogenesis


Tian J,Lambertz I,Berton TR,Rundhaug JE,Kiguchi K,Shirley SH,Digiovanni J,Conti CJ,Fischer SM,Fuchs-Young R




Has Abstract


2012-12-01 00:00:00












  • Induction and progression of the transformed phenotype in cloned rat embryo fibroblast cells: studies employing type 5 adenovirus and wild-type and mutant Ha-ras oncogenes.

    abstract::Transformation of cloned rat embryo fibroblast (CREF) cells with the wild-type 5 adenovirus (wtAd5) transforming genes E1A and E1B (which extend from 0 to 11.2 map units) results in morphologically transformed cells that exhibit an increased saturation density in monolayer culture and display an anchorage-independent ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Boylan JF,Shih TY,Fisher PB,Zimmer SG

    更新日期:1992-01-01 00:00:00

  • Connexin 32 potentiates vinblastine-induced cytotoxicity in renal cell carcinoma cells.

    abstract::We have reported that connexin (Cx) 32 gene, a member of gap junction protein family, acts as a tumor suppressor gene in human renal cell carcinoma (RCC). Of solid tumors, RCC is one of the most chemoresistant cancers, and there is no effective cancer chemotherapy against RCC at present. In this study, we examined if ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Sato H,Senba H,Virgona N,Fukumoto K,Ishida T,Hagiwara H,Negishi E,Ueno K,Yamasaki H,Yano T

    更新日期:2007-03-01 00:00:00

  • Protein phosphatase 2A is essential to maintain active Wnt signaling and its Aβ tumor suppressor subunit is not expressed in colon cancer cells.

    abstract::Canonical Wnt signaling is altered in most cases of colorectal cancer. Experimental evidence indicates that protein phosphatase 2A (PP2A) may play either positive or negative roles in Wnt signaling but its precise in vivo functions remain elusive. In this work, using colon cultured cell lines we showed that basal PP2A...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Carmen Figueroa-Aldariz M,Castañeda-Patlán MC,Santoyo-Ramos P,Zentella A,Robles-Flores M

    更新日期:2015-11-01 00:00:00

  • Characterization of the basal and carcinogen regulatory elements of the rat mdr1b promoter.

    abstract::In this report we characterized the transcriptional regulation of the rat mdr1b gene by xenobiotics. The expression of this gene was increased in primary rat hepatocytes and in the H4-II-E hepatoma cell line by exposure to carcinogens such as aflatoxin B1, N-acetoxy-2-acetylaminofluorene, and methyl methanesulfonate. ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Silverman JA,Hill BA

    更新日期:1995-05-01 00:00:00

  • Role of mitogen-activated protein kinases and Mcl-1 in apoptosis induction by withaferin A in human breast cancer cells.

    abstract::Withaferin A (WA), a bioactive constituent of Ayurvedic medicine plant Withania somnifera, is a potent apoptosis inducer in cancer cells but the mechanism of cell death induction is not fully characterized. The present study was undertaken to determine the role of mitogen-activated protein kinases (MAPK), including c-...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Hahm ER,Lee J,Singh SV

    更新日期:2014-11-01 00:00:00

  • Phenylbutyl isoselenocyanate induces reactive oxygen species to inhibit androgen receptor and to initiate p53-mediated apoptosis in LNCaP prostate cancer cells.

    abstract::Previous studies have established the in vivo bioavailability and efficacious dosages of phenylbutyl isoselenocyanate (ISC-4), a selenium-substituted isothiocyanate, against mouse xenograft models of human melanoma and colorectal cancer. To explore its potential attributes against prostate cancer, we treated human LNC...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Wu W,Karelia D,Pramanik K,Amin SG,Sharma AK,Jiang C,Lu J

    更新日期:2018-08-01 00:00:00

  • Mapping of tyrosine kinase gene family members in a Xiphophorus melanoma model.

    abstract::Xiphophorus fish have been the subject of intensive genetic research for more than 60 yr, primarily because of the availability of a number of interspecific hybrids that are malignant melanoma models with apparently simple oncogene and tumor suppressor gene determinants. The gene map of Xiphophorus is one of the most ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Morizot DC,McEntire BB,Della Coletta L,Kazianis S,Schartl M,Nairn RS

    更新日期:1998-07-01 00:00:00

  • Evidence that mutational activation of the ras genes may not be involved in aflatoxin B(1)-induced human hepatocarcinogenesis, based on sequence analysis of the ras and p53 genes.

    abstract::Exposure to aflatoxin B(1) (AFB(1)) is one of the risk factors for developing hepatoma. In rats, activation of the ras gene is a prevalent event in AFB(1)-induced hepatocarcinogenesis. It is not clear whether a similar event occurs in humans. By analysis of codon 249 of the p53 gene, six of 36 human hepatoma samples w...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Chao HK,Tsai TF,Lin CS,Su TS

    更新日期:1999-10-01 00:00:00

  • Overexpression of MDM-2 mRNA and mutation of the p53 tumor suppressor gene in bladder carcinoma cell lines.

    abstract::To investigate the importance of oncogenes and tumor suppressor genes in bladder carcinogenesis, we determined the status of the expression of the MDM-2 and p53 genes and genetic alterations in the p53 gene in five bladder carcinoma cell lines and one kidney urothelial carcinoma cell line. Overexpression of MDM-2 mRNA...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Cheng YT,Li YL,Wu JD,Long SB,Tzai TS,Tzeng CC,Lai MD

    更新日期:1995-07-01 00:00:00

  • Microarray meta-analysis defines global angiogenesis-related gene expression signatures in human carcinomas.

    abstract::Angiogenesis is a prerequisite for progression of cancers. The number of genes linked to angiogenesis suggests the existence of complex gene-networks, which remain to be elucidated. To identify angiogenesis genes deregulated in carcinomas, we performed a meta-profiling analysis of published gene expression microarray ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,meta分析


    authors: Anders M,Fehlker M,Wang Q,Wissmann C,Pilarsky C,Kemmner W,Höcker M

    更新日期:2013-01-01 00:00:00

  • Species-specific effects of the hepatocarcinogens 3'-methyl-4-dimethyl-aminoazobenzene and ortho-aminoazotoluene in mouse and rat liver.

    abstract::The effects of rat-specific hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB), mouse-specific hepatocarcinogen ortho-aminoazotoluene (OAT), non-species-specific hepatocarcinogen diethylnitrosamine (DENA), and non-carcinogenic 4'-methyl-4-dimethylaminoazobenzene (4'-MeDAB) on glucocorticoid induction of t...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Merkulova TI,Kropachev KY,Timofeeva OA,Vasiliev GV,Levashova ZB,Ilnitskaya SI,Kobzev VF,Pakharukova MY,Bryzgalov LO,Kaledin VI

    更新日期:2005-12-01 00:00:00

  • Stromal contributions to the carcinogenic process.

    abstract::Tumor-associated stromal cells are dynamic characters that endorse the carcinogenic process in a multitude of ways. The tumor microenvironment plays a crucial role throughout the tumor progression, which includes initiation, growth, invasion, and metastasis. The tumor microenvironment consists of cellular and non-cell...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审


    authors: Spaw M,Anant S,Thomas SM

    更新日期:2017-04-01 00:00:00

  • Ras-mediated intestinal epithelial cell transformation requires cyclooxygenase-2-induced prostaglandin E2 signaling.

    abstract::Ras-mediated transformation is associated with upregulation of cyclooxygenase-2 (COX-2), which in turn promotes prostaglandin E2 (PGE2) synthesis and secretion. Although recent studies have identified molecular mechanisms by which Ras mediates upregulation of COX-2, conflicting observations have been made. Furthermore...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Repasky GA,Zhou Y,Morita S,Der CJ

    更新日期:2007-12-01 00:00:00

  • Effect of energy restriction on the expression of cyclin D1 and p27 during premalignant and malignant stages of chemically induced mammary carcinogenesis.

    abstract::The restriction of energy intake has a profound inhibitory effect on carcinogenesis, yet the mechanism or mechanisms that account for this effect are unknown. In this experiment, the hypothesis tested was that energy restriction upregulates the expression of p27/kip1, a gene product associated with cell-cycle growth a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Zhu Z,Jiang W,Thompson HJ

    更新日期:1999-04-01 00:00:00

  • p28(GANK) associates with p300 to attenuate the acetylation of RelA.

    abstract::Oncoprotein p28(GANK), overexpressed in hepatocellular carcinomas (HCC), binds to RelA and retains NF-κB in the cytoplasm to suppress NF-κB transactivation. However, the mechanism has not yet been elucidated. In this study, we clarified the mechanism of NF-κB regulated by p28(GANK). p28(GANK) reduced TNF-α-induced nuc...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Ren YB,Luo T,Li J,Fu J,Wang Q,Cao GW,Chen Y,Wang HY

    更新日期:2015-12-01 00:00:00

  • Distinct roles of individual Smads in skin carcinogenesis.

    abstract::Transforming growth factor beta (TGFbeta) signaling has both tumor suppression and promotion roles. Smads are transcription factors that primarily mediate intracellular signaling for the TGFbeta superfamily. Loss of Smad2 and Smad4, but not Smad3 is common in human cancers. Given the complex nature of TGFbeta signalin...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审


    authors: Bornstein S,Hoot K,Han GW,Lu SL,Wang XJ

    更新日期:2007-08-01 00:00:00

  • Inhibition of oncogenic BRAF activity by indole-3-carbinol disrupts microphthalmia-associated transcription factor expression and arrests melanoma cell proliferation.

    abstract::Indole-3-carbinol (I3C), an anti-cancer phytochemical derived from cruciferous vegetables, strongly inhibited proliferation and down-regulated protein levels of the melanocyte master regulator micropthalmia-associated transcription factor (MITF-M) in oncogenic BRAF-V600E expressing melanoma cells in culture as well as...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Kundu A,Quirit JG,Khouri MG,Firestone GL

    更新日期:2017-01-01 00:00:00

  • Association of apoptosis with the inhibition of extracellular signal-regulated protein kinase activity in the tumor necrosis factor alpha-resistant ovarian carcinoma cell line UCI 101.

    abstract::Tumor necrosis factor-alpha (TNF alpha) can function as both an autocrine and a paracrine growth factor and may therefore play a role in ovarian tumor progression. TNF alpha initiates multiple cellular responses, many of which are mediated through the mitogen-activated protein kinase pathways, which transduce signals ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Yazlovitskaya EM,Pelling JC,Persons DL

    更新日期:1999-05-01 00:00:00

  • CLIC4, skin homeostasis and cutaneous cancer: surprising connections.

    abstract::Chloride intracellular channel 4 (CLIC4) is a putative chloride channel for intracellular organelles. CLIC4 has biological activities in addition to or because of its channel activity. In keratinocytes, CLIC4 resides in the mitochondria and cytoplasm, and CLIC4 gene expression is regulated by p53, TNF-alpha, and c-Myc...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审


    authors: Suh KS,Malik M,Shukla A,Yuspa SH

    更新日期:2007-08-01 00:00:00

  • Epidemiology and potential mechanisms of tobacco smoking and heavy alcohol consumption in pancreatic cancer.

    abstract::Tobacco smoking represents an important known cause of ductal pancreatic adenocarcinoma. Recent data from pooled analyses in consortia involving multiple case-control and cohort studies suggest that heavy (but not moderate or light) alcohol consumption also may increase pancreatic cancer risk. Animal and human evidenc...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审


    authors: Duell EJ

    更新日期:2012-01-01 00:00:00

  • Betulinic acid suppresses constitutive and TNFalpha-induced NF-kappaB activation and induces apoptosis in human prostate carcinoma PC-3 cells.

    abstract::Development of chemoresistance in androgen-refractory prostate cancer cells is partly due to constitutive activation of Rel/NF-kappaB transcription factors that regulate several cell survival and anti-apoptotic genes. In this study we examined whether betulinic acid (BetA), a pentacyclic triterpene from the bark of wh...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Rabi T,Shukla S,Gupta S

    更新日期:2008-12-01 00:00:00

  • Genetic variant rs16430 6bp > 0bp at the microRNA-binding site in TYMS and risk of sporadic breast cancer risk in non-Hispanic white women aged ≤ 55 years.

    abstract::Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T)...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Guan X,Liu H,Ju J,Li Y,Li P,Wang LE,Brewster AM,Buchholz TA,Arun BK,Wei Q,Liu Z

    更新日期:2015-04-01 00:00:00

  • Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells.

    abstract::Dietary heterocyclic aromatic amines (HCA) and polyunsaturated fatty acids (PUFA) are both believed to play a role in colon carcinogenesis, and are both substrate for the enzyme cyclooxygenase (COX). In HCA-7 cells, highly expressing isoform COX-2, we investigated the effects of PUFA on prostaglandin synthesis and DNA...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Moonen HJ,Dommels YE,van Zwam M,van Herwijnen MH,Kleinjans JC,Alink GM,de Kok TM

    更新日期:2004-07-01 00:00:00

  • Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas.

    abstract::The expression of members of the family of matrix-degrading metalloproteinases (MMPs) is believed to contribute to the complex process of invasion and metastasis. In this study, specific cDNA probes for three members of the stromelysin subfamily of MMPs--stromelysin (MMP-3), stromelysin-2 (MMP-10), and pump-1 (MMP-7)-...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: McDonnell S,Navre M,Coffey RJ Jr,Matrisian LM

    更新日期:1991-01-01 00:00:00

  • LncAPC drives Wnt/β-catenin activation and liver TIC self-renewal through EZH2 mediated APC transcriptional inhibition.

    abstract::Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis, and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver c...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Fu X,Lin J,Qin F,Yang Z,Ding Y,Zhang Y,Han L,Zhu X,Zhang Q

    更新日期:2018-03-01 00:00:00

  • Betulin induces mitochondrial cytochrome c release associated apoptosis in human cancer cells.

    abstract::We examined whether betulin, a naturally abundant compound, has anticancer functions in human cancer cells. The results showed that betulin significantly inhibited cell viability in cervix carcinoma HeLa cells, hepatoma HepG2 cells, lung adenocarcinoma A549 cells, and breast cancer MCF-7 cells with IC(50) values rangi...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Li Y,He K,Huang Y,Zheng D,Gao C,Cui L,Jin YH

    更新日期:2010-07-01 00:00:00

  • Mutational analysis of a dominant oncogene (c-Ki-ras-2) and a tumor suppressor gene (p53) in hamster lung tumorigenesis.

    abstract::In human lung cancers, alterations of both a dominant oncogene (ras) and a tumor suppressor gene (p53) have been identified. Polymerase chain reaction (PCR) analysis of mRNA was used to amplify the c-Ki-ras-2 and p53 genes from Syrian golden hamsters. The PCR products were confirmed by predicted-size analysis, probing...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Oreffo VI,Lin HW,Gumerlock PH,Kraegel SA,Witschi H

    更新日期:1992-01-01 00:00:00

  • Modulation of the oncogenic potential of beta-catenin by the subcellular distribution of plakoglobin.

    abstract::Plakoglobin (Pg) and beta-catenin are homologous proteins that function in cell-cell adhesion and signaling. The cadherin-associated form of these proteins mediates adhesion, whereas the cytosolic/nuclear form has a signaling role. Despite their interactions with common cellular partners, beta-catenin has a well-docum...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Li L,Chapman K,Hu X,Wong A,Pasdar M

    更新日期:2007-10-01 00:00:00

  • Involvement of Akt/NF-κB pathway in N6-isopentenyladenosine-induced apoptosis in human breast cancer cells.

    abstract::N(6)-isopentenyladenosine (i6A) inhibits the tumor cell growth by inducing cell apoptosis in various cancer cell lines. However, little is known regarding the mechanisms by which the drug induces cell apoptosis. In this study, we further explored the molecular mechanisms of i6A as an anticancer agent on a human breast...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Laezza C,Malfitano AM,Di Matola T,Ricchi P,Bifulco M

    更新日期:2010-10-01 00:00:00

  • Transforming activity of DNA from rat liver tumors induced by the carcinogen methyl(acetoxymethyl)nitrosamine.

    abstract::Altered c-Ha-ras genes have been frequently detected in the DNA of spontaneous or chemically induced mouse liver tumors. To determine if ras gene mutation is a frequent event during liver carcinogenesis in rats, we examined the transforming activity of DNA from liver tumors that developed in rats injected with methyl(...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章


    authors: Goyette M,Dolan M,Kaufmann W,Kaufman D,Shank PR,Fausto N

    更新日期:1988-01-01 00:00:00