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 new system for studying carcinogen-induced amplification of both endogenous and viral sequences in the SV40-transformed human keratinocyte line AG06. Treatment with carcinogens induced a transient dose-dependent amplification of the integrated SV40 sequences. The amplified sequences appeared in the extrachromosomal fraction. Treatment of these cells with carcinogens prior to methotrexate (MTX) selection increased the frequency of MTX-resistant colonies, 67% of which exhibited dihydrofolate reductase (dhfr) amplification. The abilities of five carcinogens with different DNA-damaging activities (the DNA-damaging agents N-methyl-N-nitro-N-nitrosoguanidine, mitomycin C (MMC), ultraviolet light C, and X-rays and the non-DNA-damaging agent arsenite) to induce SV40 and dhfr amplification at concentrations that result in 50% clonal survival were compared. All four DNA-damaging carcinogens (as well as growth arrest) were able to elicit some SV40 amplification, but responses varied markedly, from 1.8-fold for X-rays to sevenfold to eightfold for MMC. There was no correlation between the ability to elicit the two amplification responses. Arsenite, which did not induce SV40 amplification, was the best inducer of MTX resistance. These results point to different controls involved in the induction of viral and dhfr amplification. The signal for amplification of viral genes may be triggered by DNA damage and growth arrest, whereas amplification of dhfr, and perhaps other endogenous sequences, seems to be triggered by other signals as well.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Rossman TG,Wolosin Ddoi
10.1002/mc.2940060306subject
Has Abstractpub_date
1992-01-01 00:00:00pages
203-13issue
3eissn
0899-1987issn
1098-2744journal_volume
6pub_type
杂志文章abstract::Peptidylarginine deiminase type 4 (PAD4/PADI4) posttranslationally converts peptidylarginine to citrulline, in a process known as citrullination. Evidence suggests that PAD4 plays an essential role in pathogenesis of rheumatoid arthritis (RA). RA synovium has many features in common with tumor tissues, including abnor...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20169
更新日期:2006-03-01 00:00:00
abstract::Although carcinoma of the uterine endometrium is the most frequently diagnosed malignancy of the female reproductive tract, the molecular genetic features of this tumor have yet to be described in significant detail. Since mutations of the p53 tumor suppressor gene are the single most common genetic alteration found i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050403
更新日期:1992-01-01 00:00:00
abstract::2-Methoxyestradiol (2-ME), an endogenous metabolite of 17beta-estradiol, is present in human blood and urine. Here we show for the first time that 2-ME significantly inhibited the growth of normal prostate epithelial cells and androgen-dependent LNCaP and androgen-independent DU145 prostate cancer cells. This growth i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.1046
更新日期:2001-07-01 00:00:00
abstract::The physical gut barrier, comprised of a thick mucus layer and the epithelium, plays an important role in defense against microbes and foreign antigens. Calcium and vitamin D may be involved in maintaining the integrity of the intestinal mucosal barrier, the dysfunction of which may lead to endotoxemia and inflammatio...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1002/mc.23010
更新日期:2019-07-01 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::The E5 open reading frame (ORF) from bovine papillomavirus type 1 (BPV 1) as well as the E5 ORFs from human papillomaviruses (HPV) type 6 and type 16 have been reported to transform immortalized rodent cells. In an analysis of murine and human tumors for the presence of putative papillomavirus-related sequences, we cl...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940060204
更新日期:1992-01-01 00:00:00
abstract::The prevalence of obesity, an established risk and progression factor for postmenopausal breast cancer, remains high in US women. Activation of Akt/mammalian target of rapamycin (mTOR) signaling plays a key role in the obesity-breast cancer link. However, the impact of weight normalization in obese postmenopausal wome...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21878
更新日期:2013-06-01 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::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::The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22490
更新日期:2017-01-01 00:00:00
abstract::Obesity increases colorectal cancer (CRC) risk and progression. However, the impact of obesity on CRC in women is dependent on ovarian hormone status. The purpose of this study was to determine the interactive roles of obesity and ovarian hormones on serum markers of inflammation, cell signaling, and transplanted colo...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20720
更新日期:2011-05-01 00:00:00
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
doi:10.1002/mc.22235
更新日期:2015-12-01 00:00:00
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
doi:10.1002/mc.20786
更新日期:2012-01-01 00:00:00
abstract::Arsenic is a known human carcinogen. However, the mechanism of how arsenic induces cell transformation remains unclear. In this study, we demonstrated that long-term exposure to sodium arsenite at low-dose (2 µM) increases cell proliferation and neoplastic transformation in a mouse epidermal cell model, JB6 promotion-...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20733
更新日期:2011-07-01 00:00:00
abstract::Phloretin (Ph), which can be obtained from apples, apple juice, and cider, is a known inhibitor of the type II glucose transporter (GLUT2). In this study, real-time PCR analysis of laser-capture microdissected (LCM) human hepatoma cells showed elevated expression (>5-fold) of GLUT2 mRNA in comparison with nonmalignant...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20480
更新日期:2009-05-01 00:00:00
abstract::We previously found that the small GTPase Rheb regulates the cell-cycle inhibitor p27KIP1 (p27) in colon cancer cells by a mTORC1-independent mechanism. However, the biological function of the Rheb/p27 axis in cancer cells remains unknown. Here, we show that siRNA-mediated depletion of Rheb decreases survival of human...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22272
更新日期:2016-02-01 00:00:00
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
doi:10.1002/mc.20310
更新日期:2007-10-01 00:00:00
abstract::Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4 (LXA4 ) and resolvi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,随机对照试验
doi:10.1002/mc.22629
更新日期:2017-08-01 00:00:00
abstract::Glioblastoma (GBM) is the most aggressive and highly invasive type of astrocytic tumors. Despite advances in diagnosis and therapy, the prognosis and survival time remain poor. Identifying key mediators of tumor cell proliferation, migration, and invasion is crucial to the development of new and more effective therapi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22774
更新日期:2018-04-01 00:00:00
abstract::It becomes feasible to perform genome-wide differential gene or protein expression in the post genome era. However, little has been addressed on the effects of external stresses and microenvironment alterations on the outcomes of gene and protein expression. To identify downregulated genes during hepatoma development,...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20095
更新日期:2005-06-01 00:00:00
abstract::Adenocarcinoma accounts for ∼40% of lung cancer, equating to ∼88 500 new patients in 2015, most of who will succumb to this disease, thus, the public health burden is evident. Unfortunately, few early biomarkers as well as effective therapies exist, hence the need for novel targets in lung cancer treatment. We previou...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22475
更新日期:2017-01-01 00:00:00
abstract::We evaluated whether high-fat diet (HFD), in the absence of increased calorie intake, increases colon cancer growth and metastasis. Four-week-old male BALB/c mice were fed on an HFD (60 kcal% fat) or control diet (10 kcal% fat) for 16 wk, after which CT26 colon cancer cells were subcutaneously injected into the right ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20856
更新日期:2012-11-01 00:00:00
abstract::Gliomas are common, aggressive central nervous system tumors with poor overall survival rates. Despite improvements in neurosurgery, chemotherapy, and radiotherapy, the outcomes of patients with malignant gliomas remain poor. Therefore, increased knowledge of the molecular mechanisms that regulate glioma progression i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22834
更新日期:2018-09-01 00:00:00
abstract::Deregulation of insulin-like growth factor-1 receptor (IGF-1R) and focal adhesion kinase (FAK) signaling pathways plays an important role in cancer cell proliferation and metastasis. In pancreatic cancer cells, the crosstalk and compensatory mechanisms between these two pathways reduce the efficacy of the treatments t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20590
更新日期:2010-02-01 00:00:00
abstract::Betanin, also called beetroot red, has been extensively used as a food colorant. In this study, the chemopreventive activity of betanin by oral consumption was investigated in two mouse lung tumor models. Vinyl carbamate (VC) and benzo(a)pyrene (B(a)P) were used to induce lung tumors, and female A/J mice were treated ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21907
更新日期:2013-09-01 00:00:00
abstract::Cytokines are considered to play an important role in tumor pathogenesis and progression, and recent studies have demonstrated that a variety of forms, including interleukins (ILs) and transforming growth factor-beta(s) (TGF-beta(s)), may regulate tumors. In the present study, the expression of TGF-beta isoforms and I...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2002-02-01 00:00:00
abstract::The role of estrogen and the estrogen receptor (ER) in the induction and promotion of tumors was investigated by using transgenic MT-mER mice, which overexpress the ER. It was hypothesized that because of this abnormal expression of the ER, the reproductive-tract tissues of the MT-mER mice may be more susceptible to t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199708)19:4<236::aid-mc4>3
更新日期:1997-08-01 00:00:00
abstract::We examined the expression of two groups of matrix metalloproteinases (MMPs), stromelysin and interstitial collagenase, in human skin cancer by northern blot analysis and in situ hybridization. Stromelysin-3 (ST-3) mRNA was overexpressed more than tenfold in 17 of 19 (89%) specimens of basal cell carcinoma (BCC) but i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940090105
更新日期:1994-01-01 00:00:00
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
doi:10.1002/(sici)1098-2744(199807)22:3<150::aid-mc2>3
更新日期:1998-07-01 00:00:00
abstract::Atypical adenomatous hyperplasia (AAH) of the prostate is characterized by lobular proliferation of closely packed small acini. It is hypothesized that AAH is a precursor lesion for low-grade prostate cancer arising from the transition zone. Telomere dysfunction is common during malignant transformation of epithelia. ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23009
更新日期:2019-07-01 00:00:00