Abstract:
:An increased neuroendocrine (NE) cell population in prostate cancer is associated with more aggressive disease and recurrence after androgen-deprivation therapy, although the mechanism responsible is unknown. In this study, we report that the treatment of LNCaP cells with epidermal growth factor (EGF) in the presence of LY294002, an inhibitor of the phosphoinositol 3'-kinase (PI3K)-AKT pathway, induced an increase of levels and activity of ErbB2. Under these conditions, we also observed cell survival and NE differentiation. When we treated with wortmannin, another PI3K inhibitor, or we knocked down PI3K or AKT isoforms in the presence of EGF, ErbB2 up-regulation was not observed, suggesting that the increase of ErbB2 induced by EGF plus LY294002 is not mediated by the PI3K-Akt pathway. Other targets of LY294002 were also discounted. We also show that ErbB2 up-regulation is directly involved in neuroendocine differentiation but not in cell survival as ErbB2 levels increased in parallel with NE differentiation marker levels, whereas ErbB2 knockdown reduced them; other NE differentiation inducers also increased the ErbB2 levels and the immunohistochemical analysis of prostate cancer samples showed colocalization of ErbB2 and chromogranin A. We found that, in LNCaP cells, EGF in combination with LY294002 increased ErbB2 levels by a PI3K/AKT-independent mechanism and that this increase was associated with the acquisition of a NE phenotype. These results suggest that is worth reconsidering ErbB2 as a drug target in prostate cancer and this should be kept in mind when designing new clinical schedules for the treatment of this disease.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Cortés MA,Cariaga-Martinez AE,Lobo MV,Martín Orozco RM,Motiño O,Rodríguez-Ubreva FJ,Angulo J,López-Ruiz P,Colás Bdoi
10.1093/carcin/bgs139subject
Has Abstractpub_date
2012-06-01 00:00:00pages
1169-77issue
6eissn
0143-3334issn
1460-2180pii
bgs139journal_volume
33pub_type
杂志文章相关文献
CARCINOGENESIS文献大全abstract::N-nitrosopiperidine (NPIP) is a potent esophageal carcinogen in rats whereas structurally similar N-nitrosopyrrolidine (NPYR) induces liver, but not esophageal tumors. NPIP is a possible causative agent for human esophageal cancer. Our goal is to explain mechanistically these differing carcinogenic activities in the e...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/24.2.291
更新日期:2003-02-01 00:00:00
abstract::Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants with high carcinogenic potencies that have been linked to the etiology of human cancers through their presence in cigarette smoke and environmental mixtures. They are metabolically activated in cells by cytochrome P450 enzymes and/or perox...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.10.1885
更新日期:1999-10-01 00:00:00
abstract::The possibility that ascorbic acid, as a nucleophile, may inhibit mutagenicity induced by electrophilic metabolites of N-nitroso compounds was examined. In vitro data are presented to show that ascorbic acid does not decrease the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in a modified Ames bacterial ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/6.11.1593
更新日期:1985-11-01 00:00:00
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...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/23.7.1209
更新日期:2002-07-01 00:00:00
abstract::Certain hexavalent chromium [Cr(VI)] compounds are implicated as occupational respiratory carcinogens. Cr(VI) induces a broad spectrum of DNA damage, but Cr(VI)-induced DNA double-strand breaks (DSBs) have not been reported. Previously we found that Cr(VI) activates the ataxia telangiectasia mutated (ATM) kinase. ATM ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgh242
更新日期:2004-11-01 00:00:00
abstract::Androgens and estrogens may play a role in gastric cancer etiology. To investigate the association of gastric cancer with single-nucleotide polymorphisms (SNPs) in six genes (COMT, CYP1B1, CYP17A1, CYP19A1, HSD17B1 and SHBG) involved in estrogen and androgen synthesis and metabolism, 58 haplotype-tagging SNPs were gen...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn258
更新日期:2009-01-01 00:00:00
abstract::Since its discovery, the E3 ubiquitin ligase E6-associated protein (E6AP) has been studied extensively in two pathological contexts: infection by the human papillomavirus (HPV), and the neurodevelopmental disorder, Angelman syndrome. Vital biological links between E6AP and other viruses, namely hepatitis C virus and e...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/bgz072
更新日期:2019-07-06 00:00:00
abstract::MicroRNAs (miRNAs or miR) have been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. The miR-124 was reported to be attenuated in several tumors, such as glioma, medulloblastoma and hepatocellular carcinoma. However, its role in cancer remains greatly elusive. In this study, we show ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs383
更新日期:2013-03-01 00:00:00
abstract::A number of drug-metabolizing systems were measured in hyperplastic noduli from the livers of rats receiving 2-acetyl-aminofluorene in their diet and compared with corresponding activities in control liver. The level of microsomal cytochrome P-450 is reduced 54% in the nodular tissue, while 5 activities catalyzed by t...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/4.5.577
更新日期:1983-01-01 00:00:00
abstract::A growing body of evidence from human and animal cancer cytogenetics studies indicates that aneuploidy is an important chromosome change in carcinogenesis. To understand the role of this genetic phenomenon during the first steps of an experimental cancer model, molecular and cellular techniques were combined. A sequen...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.8.1825
更新日期:1995-08-01 00:00:00
abstract::Losses of heterozygosity (LOH) of the short arm of chromosome 19 are frequent in lung cancer, suggesting that one or more tumor suppressor genes are present in this region. The LKB1 gene, also called STK11, is somatically inactivated through point mutations and large deletions in lung tumors, demonstrating that LKB1 i...
journal_title:Carcinogenesis
pub_type: 杂志文章,评审
doi:10.1093/carcin/bgp035
更新日期:2009-04-01 00:00:00
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...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl078
更新日期:2006-12-01 00:00:00
abstract::DNA double-strand break (DSB) repair is an important mechanism underlying chemotherapy resistance in human cancers. Dicer participates in DSB repair by facilitating homologous recombination. However, whether Dicer is involved in non-homologous end joining (NHEJ) remains unknown. Here, we addressed whether Dicer regula...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgx059
更新日期:2017-09-01 00:00:00
abstract::The use of naturally occurring botanicals with substantial antioxidant activity to afford protection to human skin against UV damage is receiving increasing attention. The green tea constituent (-)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant and has shown remarkable preventive effects against photocarcin...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/22.2.287
更新日期:2001-02-01 00:00:00
abstract::The pulmonary adenoma susceptibility 1 (Pas1) gene affects susceptibility to the development of lung adenomas in mice with a subset of the adenomas progressing to adenocarcinoma (ADC). In this study, genotype distributions for 10 polymorphisms in the human counterparts for three mouse candidate Pas1 genes, KRAS, CASC1...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn048
更新日期:2008-05-01 00:00:00
abstract::A diet deficient in choline when fed to rats for as few as 3 days resulted in liver DNA damage. The damage could be monitored as alkali-labile lesions using alkaline-sucrose gradients as well as alkaline elution technique. The DNA damage disappeared when the choline-deficient diet was replaced by a choline-supplemente...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/7.10.1677
更新日期:1986-10-01 00:00:00
abstract::Although Epstein-Barr virus (EBV) infection is widely distributed, certain EBV-driven malignancies are geographically restricted. EBV-associated Burkitt's lymphoma (eBL) is endemic in children living in sub-Saharan Africa. This population is heavily exposed to food contaminated with the mycotoxin aflatoxin B1 (AFB1). ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgv142
更新日期:2015-11-01 00:00:00
abstract::Women who carry the BRCA mutation are at high lifetime risk of breast cancer, but there is no consensus regarding an effective and safe chemoprevention strategy. A large body of evidence suggests that 3,3-diindolylmethane (DIM), a dimer of indole-3-carbinol found in cruciferous vegetables, can potentially prevent carc...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgaa050
更新日期:2020-10-15 00:00:00
abstract::The modulating effects of dietary feeding of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) during the postinitiation phase on colon carcinogenesis initiated with azoxymethane (AOM) were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.12.2957
更新日期:1995-12-01 00:00:00
abstract::To evaluate the significance of C-C chemokine receptor type 5 (CCR5) in lung tumor development, we compared carcinogen-induced tumor growth in CCR5 knockout (CCR5(-/-)) mice and wild-type (CCR5(+/+)) mice. CCR5(-/-) mice showed reduced urethane (1g/kg)-induced tumor incidence when compared with those of CCR5(+/+) mice...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgs265
更新日期:2012-12-01 00:00:00
abstract::Ouabain resistance (ouar) and 6-thioguanine resistance (6-TGr) mutation frequencies were measured in Chinese hamster ovary cells after treatment with N-ethyl-N-nitrosourea (ENU) for varying periods of time. Maximal mutation frequency at the Na+/K+ ATPase gene locus (ouar mutations) was attained within 5 min of exposur...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/8.1.25
更新日期:1987-01-01 00:00:00
abstract::It has been proposed that extremely low frequency magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin carcinogenesis in mic...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/20.4.685
更新日期:1999-04-01 00:00:00
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...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn011
更新日期:2008-04-01 00:00:00
abstract::Occupational nitrosamine exposures from a rubber vehicle seal (VS) curing operation were compared with the peripheral blood lymphocyte concentrations of two nitrosamine-related DNA adducts, N(7)-methylguanine (N(7)mdG) and O(6)-methylguanine (O(6)mdG), and with the activity of the enzyme that repairs O(6)mdG adducts, ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/21.1.29
更新日期:2000-01-01 00:00:00
abstract::Common genetic variation may play an important role in altering lung cancer risk. We conducted a pathway-based candidate gene evaluation to identify genetic variations that may be associated with lung cancer in a population-based case-control study in Xuan Wei, China (122 cases and 111 controls). A total of 1260 singl...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgn178
更新日期:2008-10-01 00:00:00
abstract::Thioredoxin reductases (TrxRs) catalyse the NADPH-dependent reduction of thioredoxin and play an important role in multiple cellular events related to carcinogenesis including cell proliferation, apoptosis and cell signaling. We have used human hepatoma HepG2 cells to examine the regulation of TrxRs by isothiocyanate ...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/24.3.497
更新日期:2003-03-01 00:00:00
abstract::Occupational exposure to styrene was studied in nine workers of a hand lamination plant in Bohemia. Personal dosimeters were used to monitor the styrene workplace exposure, and the levels of styrene in blood and mandelic acid in urine were measured. Blood samples were taken at four occasions during a 7 month period to...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/16.7.1473
更新日期:1995-07-01 00:00:00
abstract::The MDM2 protein negatively regulates p53 expression level in modulating DNA repair, cell-cycle control, cell growth and apoptosis. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter protein expression and may, thus, play a role in carcinogenesis. To test our hypothesis that the MDM2 promot...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgl047
更新日期:2006-10-01 00:00:00
abstract::The role of O-GlcNAc transferase (OGT) in gene regulation and tumor invasion is poorly understood. Here, we have identified several previously undiscovered OGT-interacting proteins, including the PRMT5/WDR77 complex, the PRC2 complex, the ten-eleven translocation (TET) family, the CRL4B complex and the nucleosome remo...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/bgy097
更新日期:2018-10-08 00:00:00
abstract::Hairless mice were given 5 topical applications of 470 nmol 20-methylcholanthrene (MCA) at one week intervals. In one experimental group the MCA was dissolved in reagent grade acetone alone, in another group it was dissolved in a mixture consisting of 50% acetone and 50% dimethyl sulfoxide (DMSO). A control group rece...
journal_title:Carcinogenesis
pub_type: 杂志文章
doi:10.1093/carcin/2.11.1129
更新日期:1981-01-01 00:00:00