Abstract:
:The INK4a/ARF locus encodes two distinct tumor suppressors, p16INK4a and p14ARF. Although the contribution of p16INK4a to human tumorigenesis through point mutation, deletion, and hypermethylation has been widely documented, little is known about specific p14ARF lesions and their consequences. Recent data indicate that p14ARF suffers inactivation by promoter hypermethylation in colorectal cancer cells. Because it is known that p14ARF prevents MDM2 nucleocytoplasmic shuttling and thus stabilizes p53 by attenuating MDM2-mediated degradation, we studied the relationship of p14ARF epigenetic silencing to the expression and localization of MDM2 and p53. Cancer cell lines with an unmethylated p14ARF promoter showed strong nuclear expression of MDM2, whereas in a colorectal cell line with p14ARF hypermethylation-associated inactivation, MDM2 protein was also seen in the cytosol. Treatment with the demethylating agent 5-aza-2'-deoxycytidine was able to reinternalize MDM2 to the nucleus, and p53 expression was restored. No apparent changes in retinoblastoma localization were observed. We also studied the profile of p14ARF promoter hypermethylation in an extensive collection of 559 human primary tumors of different cell types, observing that in colorectal, gastric, renal, esophageal, and endometrial neoplasms and gliomas, aberrant methylation of p14ARF was a relatively common epigenetic event. MDM2 expression patterns revealed that lack of p14ARF promoter hypermethylation was associated with tumors showing exclusive nuclear MDM2 staining, whereas MDM2 cytosolic staining was frequently observed in neoplasms with aberrant p14ARF methylation. Taken together, these data support that epigenetic silencing of p14ARF by promoter hypermethylation is a key mechanism in the disturbance of the MDM2 nuclear localization in human cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Esteller M,Cordon-Cardo C,Corn PG,Meltzer SJ,Pohar KS,Watkins DN,Capella G,Peinado MA,Matias-Guiu X,Prat J,Baylin SB,Herman JGsubject
Has Abstractpub_date
2001-04-01 00:00:00pages
2816-21issue
7eissn
0008-5472issn
1538-7445journal_volume
61pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of c...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-1982
更新日期:2004-02-01 00:00:00
abstract::To study the relationships between different DNA repair pathways, we established a set of clones in which one specific DNA repair gene was silenced using long-term RNA interference in HeLa cell line. We focus here on genes involved in either nucleotide excision repair (XPA and XPC) or nonhomologous end joining (NHEJ; ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3371
更新日期:2007-03-15 00:00:00
abstract::Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-1883
更新日期:2011-12-01 00:00:00
abstract::Gene expression signatures generated from DNA microarray analyses have shown promise as predictive biomarkers of clinical outcome. In this study, we determined a high-risk signature for disease recurrence using formalin-fixed head and neck squamous cell carcinoma (HNSCC) tumors and compared the results with an indepen...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1213
更新日期:2006-08-15 00:00:00
abstract::12-O-Tetradecanoylphorbol-13-acetate (TPA) is widely used as a tumor promoter with organotropy in skin and esophagus. TPA-induced, organ-specific tumor promotion is not correlated with the distribution of its receptor, protein kinase C (PKC). Using five administration methods (painting, drinking, gavage feeding, i.p. ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-05-15 00:00:00
abstract::Exposures to carcinogens present in the diet, in cigarette smoke, or in the environment have been associated with increased risk of bladder and colorectal cancer. The aromatic amines and their metabolites, a class of carcinogen implicated in these exposures, can be N- or O-acetylated by the NAT1 and NAT2 enzymes. Acet...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-15 00:00:00
abstract::Fatigue is the most common symptom of cancer at diagnosis, yet causes and effective treatments remain elusive. As tumors can be highly inflammatory, it is generally accepted that inflammation mediates cancer-related fatigue. However, evidence to support this assertion is mostly correlational. In this study, we directl...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-2168
更新日期:2018-02-01 00:00:00
abstract::Melanoma differentiation associated gene-7/interleukin-24 (Mda-7/IL-24), a novel member of the IL-10 family of cytokines, uniquely displays cancer-specific apoptosis-inducing activity. Positive results in ongoing phase I/II clinical trials have strengthened the possibility of its utilization as a cancer gene therapeut...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-04-0200
更新日期:2004-05-01 00:00:00
abstract::In vitro experiments selected optimal conditions to radiolabel with 131I the whole immunoglobulin and F(ab')2 fragments of the monoclonal antibody (MoAb) 225.28S to a high-molecular-weight melanoma-associated antigen (HMW-MAA). Injection of the radiolabeled whole immunoglobulin and F(ab')2 fragments of the MoAb 225.28...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-07-01 00:00:00
abstract::The pathogenetic relationship between high-grade prostatic intraepithelial neoplasia (PIN), prostatic carcinoma, and metastases is poorly understood. We used fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, 10, 12, and Y to evaluate numeric chromosomal anomalies in PIN (6...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-15 00:00:00
abstract::Microarray gene expression profiling is a powerful tool for generating molecular cancer classifications. However, elucidating biological insights from these large data sets has been challenging. Previously, we identified a gene expression-based classification of primary uveal melanomas that accurately predicts metasta...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-4196
更新日期:2006-05-01 00:00:00
abstract::Early growth-response (EGR) genes are nuclear transcription factors that are implicated in regulating cell proliferation. Because these genes show divergent expression in various human tumors, we sought to determine their expression in nonmalignant and malignant prostate tissues. Total RNA extracted from prostate tiss...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::Two malignant sublines, M4 and RMS4 , were previously derived from the recloned L6 line of rat myogenic cells. Comparative studies in tissue culture and inoculation into suckling rats indicated that M4 cells and RMS4 cells may be considered as low-malignant and high-malignant cells, respectively, while L6 cells are no...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract::Protein kinase C delta (PKCdelta), a Ca(2+)-independent, phospholipid-dependent serine/threonine kinase, is among the novel PKCs (delta, epsilon, and eta) expressed in mouse epidermis. We reported that FVB/N transgenic mice that overexpress ( approximately 8-fold) PKCdelta protein in basal epidermal cells and cells of...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2684
更新日期:2006-01-15 00:00:00
abstract::Leucine-rich repeat-containing 3B (LRRC3B) is an evolutionarily highly conserved leucine-rich repeat-containing protein, but its biological significance is unknown. Using restriction landmark genomic scanning and pyrosequencing, we found that the promoter region of LRRC3B was aberrantly methylated in gastric cancer. G...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0667
更新日期:2008-09-01 00:00:00
abstract::Interleukin-2-based regimens of biological therapy have shown some clinical promise for the treatment of kidney cancer in humans, although the mechanisms responsible for tumor regression occurring in these patients remain unclear. Preclinical insight into these mechanisms is limited by a paucity of orthotopic animal m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-08-15 00:00:00
abstract::The present work compared the blood variations in some committed stem cells (CSC), and corresponding differentiated WBC during the first three courses of a 6-day sequential chemotherapy given to 16 breast cancer patients for 28 days each. The granulomonocytic and lymphocytic colony-forming unit levels in blood were si...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::The osteolytic bone destruction associated with breast cancer skeletal metastases represents a serious and incurable clinical condition. However, the molecular mechanisms regulating tumor cell expression of factors involved in the generation of osteolytic disease remain elusive. We demonstrated recently that breast ca...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-03-3851
更新日期:2004-07-01 00:00:00
abstract::The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor-induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1898
更新日期:2007-05-01 00:00:00
abstract::The chemotherapeutic effect of B859-35, the (-)-enantiomer of dihydropyrine 3-methyl-5-3-(4,4-diphenyl-1-piperidinyl)-propyl-1,4-dihydro-2,6-dimethy l-4- (3-nitrophenyl)-pyridine-3,5-dicarboxylate-hydrochloride (niguldipine), was tested on tumors induced in Syrian golden hamsters by N-nitrosodiethylamine (DEN). Periph...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::We clarified the role of mold exposure in pituitary tumor induction using 53 germ-free Wistar rats exposed before birth and continually exposed thereafter, to Aspergillus versicolor alone. Rats were autopsied at 540 to 730 days. Untreated germ-free controls were autopsied on day 730. Thirty-three of the 53 monoassocia...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-01-15 00:00:00
abstract::Epithelial to mesenchymal transition occurs during embryologic development to allow tissue remodeling and is proposed to be a key step in the metastasis of epithelial-derived tumors. The miR-200 family of microRNAs plays a major role in specifying the epithelial phenotype by preventing expression of the transcription ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-1942
更新日期:2008-10-01 00:00:00
abstract::A mouse IgG2a monoclonal antibody, SWA20, defining a tumor-associated cell surface antigen on small cell carcinoma of the lung (SCC) was generated. The reactivity of the antibody with cell lines was examined by indirect immunofluorescence staining and solid phase radioimmunoassay and the reactivity with tissues by imm...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::The effect of culture conditions on the glutamylation of methotrexate by intact H35 hepatoma cells and folylpolyglutamate synthetase (FPGS) activity in the corresponding crude extracts has been examined. The rate of cellular glutamylation of methotrexate observed in rapidly dividing cultures was 4-fold higher than con...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Expression of the c-Myc oncoprotein is affected by conserved threonine 58 (T58) and serine 62 (S62) phosphorylation sites that help to regulate c-Myc protein stability, and altered ratios of T58 and S62 phosphorylation have been observed in human cancer. Here, we report the development of 3 unique c-myc knock-in mice ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-1032
更新日期:2011-02-01 00:00:00
abstract::High amounts of nitric oxide (NO) produced by activated macrophages or NO donors are required to induce cytotoxicity and apoptosis in pathogens and tumor cells. High concentrations of NO may lead to nonspecific toxicity thereby limiting the use of NO donors in the treatment of cancer. In this study, we tested the poss...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-06-15 00:00:00
abstract::The relative amounts of HLA-A,B,C antigens, beta 2-microglobulin (beta 2m), and trophoblast antigens (Trop-1 and Trop-2) were determined on nine choriocarcinoma cell lines including seven lines of gestational origin and two lines of nongestational origin (from ovary and stomach) by quantitative immunofluorescence anal...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::Physiological cell conditions, such as glucose deprivation and hypoxia, play a role in developing drug resistance in solid tumors. These tumor-specific conditions cause decreased expression of DNA topoisomerase IIalpha (topo IIalpha), rendering cells resistant to topo II-targeted drugs, such as etoposide and doxorubic...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract::Untargeted effects of ionizing radiation (de novo effects in the unirradiated descendants or neighbors of irradiated cells) challenge widely held views about the mechanisms of radiation-induced DNA damage with implications for the health consequences of radiation exposures particularly in the context of the induction ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0834
更新日期:2005-07-01 00:00:00
abstract::The anthracycline antineoplastic agents Adriamycin and N-trifluoroacetyl-Adriamycin-14-valerate were assayed in vivo and in vitro for ability to produce DNA lesions recognized by the UVRABC endonuclease, a DNA repair enzyme of Escherichia coli which recognizes large, bulky lesions in DNA. We found that, while both dru...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-08-01 00:00:00