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 Carcinogjournal_title
Molecular carcinogenesisauthors
Strömblad S,Eriksson LC,Andersson Gdoi
10.1002/mc.2940100207subject
Has Abstractpub_date
1994-06-01 00:00:00pages
97-104issue
2eissn
0899-1987issn
1098-2744journal_volume
10pub_type
杂志文章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
更新日期:2011-08-01 00:00:00
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
更新日期:2001-08-01 00:00:00
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
更新日期:2014-01-01 00:00:00
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
更新日期:2004-10-01 00:00:00
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
更新日期:2018-06-01 00:00:00
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
更新日期:2013-04-01 00:00:00
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
更新日期:2018-08-01 00:00:00
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
更新日期:2008-08-01 00:00:00
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
更新日期:2016-12-01 00:00:00
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
更新日期:1989-01-01 00:00:00
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
更新日期:1989-01-01 00:00:00
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
更新日期:1992-01-01 00:00:00
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
更新日期:2017-06-01 00:00:00
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
更新日期:1994-09-01 00:00:00
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
更新日期:2016-11-01 00:00:00
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
更新日期:2004-11-01 00:00:00
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
更新日期:2013-04-01 00:00:00
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
更新日期:2008-02-01 00:00:00
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
更新日期:1989-01-01 00:00:00
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
更新日期:2020-10-01 00:00:00
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
更新日期:2005-02-01 00:00:00
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
更新日期:2010-10-01 00:00:00
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
更新日期:2015-09-01 00:00:00
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
更新日期:2020-07-01 00:00:00
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
更新日期:1999-12-01 00:00:00
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
更新日期:2018-03-01 00:00:00
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
更新日期:2019-09-01 00:00:00
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
更新日期:2017-05-01 00:00:00
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
更新日期:2007-07-01 00:00:00
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:
更新日期:2000-11-01 00:00:00