Abstract:
:Although fibroblast growth factor (FGF) signals are strongly associated with malignancy, limited information is available regarding the role of the FGF9 signal in colorectal cancer (CRC). In this study, we investigated the frequency of FGF9 amplification in CRC clinical specimens and the association between the FGF9 gene and resistance to anti-EGFR therapies. In clinical samples, an FGF9 copy number gain of >5 copies was observed at a frequency of 8/145 (5.5%) and tended to be related to wild-type KRAS (7/96, 7.3%). Furthermore, FGF9 amplification was not observed in any of the samples from the 15 responders to anti-EGFR therapies but was observed in one sample from the seven non-responders with wild-type KRAS, and two samples from non-responders also had high FGF9 mRNA expression levels. FGF9 amplification was validated using a fluorescence in situ hybridization (FISH) analysis, and FGF9-amplified sections showed readily detectable signals originating from FGF9 protein when examined using immunohistochemistry. In both the in vitro and in vivo experiments using FGF9-overexpressing CRC cell lines, FGF9 overexpression induced strong resistance to anti-EGFR therapies via the enforced FGFR signal, and this resistance was cancelled by the application of an FGFR inhibitor. Considering these results, the FGF9 gene may play an important role in resistance to anti-EGFR therapies in patients with CRC, and such resistance might be overcome by combined treatment with an anti-FGFR inhibitor. These findings strongly encourage the development of FGFR-targeted therapy for CRC patients with FGF9 gene upregulation. © 2016 Wiley Periodicals, Inc.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Mizukami T,Togashi Y,Naruki S,Banno E,Terashima M,de Velasco MA,Sakai K,Yoneshige A,Hayashi H,Fujita Y,Tomida S,Nakajima TE,Fujino T,Boku N,Ito A,Nakagawa K,Nishio Kdoi
10.1002/mc.22476subject
Has Abstractpub_date
2017-01-01 00:00:00pages
106-117issue
1eissn
0899-1987issn
1098-2744journal_volume
56pub_type
杂志文章abstract::The relationship between thyroid hormone (triiodothyronine, T(3)) and breast cancer is unclear. We studied the effect of the c-erbA/TR alpha proto-oncogene encoding a functional T(3) receptor (TR alpha 1), of its ligand T(3), and of its retroviral, mutated counterpart, the v-erbA oncogene, on the proliferation capacit...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10046
更新日期:2002-05-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) plays an important role in the development and progression of lung cancer. A previous report noted that an increased number of polymorphic CA repeats in the first intron of the EGFR gene results in decreased transcriptional activity. To estimate the association of the length of ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20285
更新日期:2007-05-01 00:00:00
abstract::We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or prolonged exposure to low-dose H(2)O(2) or CdCl(2). Stable transformation was confirmed by an anchorage-independence assay. The JB6P+ transformants formed more colonies (approximately six folds) in soft agar as compared to their JB6P+ par...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20410
更新日期:2008-07-01 00:00:00
abstract::Dishevelled-3 (Dvl-3) and p120-catenin (p120ctn) have abnormal expression in non-small cell lung cancer (NSCLC), which is associated with poor prognosis. Dvl-3 upregulates p120ctn transcription in NSCLC cells, but the mechanism is unknown. Here we transiently transfected Dvl-3 cDNA to NSCLC cells. Dvl-3 transfection i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22196
更新日期:2015-06-01 00:00:00
abstract::An allelotype analysis of lung tumors in mouse hybrids was conducted to identify common regions of allelic loss. By using 50 informative genetic markers, the autosomes of 36 (A/J x C3H/HeJ) F1 adenocarcinomas were examined. Additional adenocarcinomas from as many as 72 (C3H/HeJ x A/J) F1 and 15 (BALB/cJ x DBA/2J) F1 h...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199606)16:2<83::AID-MC4>3.
更新日期:1996-06-01 00:00:00
abstract::It has been established that retinoids exert some of their effects on cell differentiation and malignant phenotype reversion through the interaction with different members of the protein kinase C (PKC) family. Till nowadays the nature and extension of this interaction is not well understood. Due to the cytostatic and ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22181
更新日期:2015-10-01 00:00:00
abstract::RAD51D, a paralog of the mammalian RAD51 gene, contributes towards maintaining genomic integrity by homologous recombination DNA repair and telomere maintenance. A RAD51D variant, E233G, was initially identified as a potential susceptibility allele in high-risk, site-specific, familial breast cancer. We describe in th...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20545
更新日期:2009-07-01 00:00:00
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
doi:10.1002/mc.2940010108
更新日期:1988-01-01 00:00:00
abstract::Potassium chromate induced the formation of DNA-protein complexes in cultured Chinese hamster ovary cells. The DNA-protein complexes were isolated by ultracentrifugal sedimentation in the presence of 2% sodium dodecyl sulfate (SDS) and 5 M urea. Two-dimensional SDS-polyacrylamide gel electrophoresis analysis of the ch...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010208
更新日期:1988-01-01 00:00:00
abstract::Sel-1-like (SEL1L) is a putative tumor suppressor gene that is significantly downregulated in human pancreatic ductal adenocarcinoma (PDA). The mechanism of the downregulation is unclear. Here, we investigated whether aberrantly upregulated microRNAs (miRNAs) repressed the expression of SEL1L. From reported miRNA micr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22023
更新日期:2014-09-01 00:00:00
abstract::The metalloproteinase matrilysin is widely expressed in the epithelial tumor cells of malignant colorectal adenocarcinomas. Approximately 50% of benign adenomas also express low levels of matrilysin that is focally localized. The expression of stromelysin-1, stromelysin-3, and gelatinase A was observed in the stromal ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940100404
更新日期:1994-08-01 00:00:00
abstract::It is well known that the TP53 gene considerably influences on DNA repair processes. Polymorphisms in the TP53 gene, particularly the well-known Arg72Pro in codon 72 of exon 4 (Ex4+119 G>C; rs1042522), can modify the functionality of the p53 protein and activation of DNA repair. Actually, polymorphic variants Arg and ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20633
更新日期:2010-06-01 00:00:00
abstract::Tumor progression is a multistep process, which enables cells to evolve from benign to malignant tumors. This progression has been suggested to depend on six essential characteristics identified as the "hallmarks of cancer," which include: self-sufficiency in growth signals, insensitivity to growth-inhibitory signals,...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20105
更新日期:2005-08-01 00:00:00
abstract::Tamoxifen (TAM) is widely used in the treatment and prevention of breast cancer. There is clear evidence that cytochrome P450 (CYP) 3A enzymes play an important role in TAM metabolism, resulting in metabolites that lead to formation of TAM-DNA adducts. We have investigated the effect of CYP3A2 antisense (AVI-4472) exp...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20143
更新日期:2006-02-01 00:00:00
abstract::Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cance...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20664
更新日期:2010-10-01 00:00:00
abstract::Hypoxia is a critical event in solid tumor development, invasion, and metastasis. Cellular adaptation to hypoxic microenvironment is essential for tumor progression and is largely mediated by hypoxia-inducible factor-1α (HIF-1α) through coordinated regulation of hypoxia-responsive genes. In this study, we found that m...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20678
更新日期:2011-10-01 00:00:00
abstract::This study examines the relationship between p53 immunostaining and direct sequencing of polymerase chain reaction (PCR) products in 61 gliomas. Glioma tissues obtained from patients at surgery were analyzed immunohistochemically with the monoclonal antibody PAb1801 to detect p53 protein abnormalities. Amplified p53 c...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199601)15:1<1::AID-MC1>3.0
更新日期:1996-01-01 00:00:00
abstract::MAP1S (originally named C19ORF5) is a widely distributed homolog of neuronal-specific MAP1A and MAP1B, and bridges autophagic components with microtubules and mitochondria to affect autophagosomal biogenesis and degradation. Mitochondrion-associated protein LRPPRC functions as an inhibitor for autophagy initiation to ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22193
更新日期:2015-10-01 00:00:00
abstract::The ubiquitin-proteasome pathway is fundamental to synchronized continuation of many cellular processes, for example, cell-cycle progression, stress response, and cell differentiation. Recent studies have shown that the ubiquitin-proteasome pathway functions in the regulation of nucleotide excision repair (NER) in yea...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20065
更新日期:2005-01-01 00:00:00
abstract::We investigated the in vitro effects of pyrogallol on cell growth, cell cycle regulation, and apoptosis in HeLa cells. Pyrogallol inhibited the growth of HeLa cells with an IC(50) of approximately 45 microM. Pyrogallol induced arrest during all phases of the cell cycle and also very efficiently resulted in apoptosis i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20369
更新日期:2008-02-01 00:00:00
abstract::Integrin alpha6beta4 is altered in many neoplastic cells, but no data exist to show this happens in esophageal neoplasms. To examine the expression of this integrin in rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine (NMBA), (alpha6 and beta4 expression was evaluated in normal esophageal epithelium, ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::Gap junctions are cellular structures which permit direct exchanges of small molecules from cytoplasm to cytoplasm in most of the cells of metazoan organisms. For four decades, it has been observed that the inhibition of this type of intercellular communication is often associated with tumorigenesis. The assumption th...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20393
更新日期:2008-05-01 00:00:00
abstract::Heat shock protein 60 (HSP60) overexpresses in various types of cancer, but its expression levels and functions in hepatocellular carcinoma (HCC) are still in dispute. We aim to clarify this issue and examine whether HSP60 could be a therapeutic target for HCC. We found drastically enhanced cell apoptosis and suppress...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22827
更新日期:2018-09-01 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::Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. The colonic mucosa constitutes a critical barrier and a major site of immune regulation. The immune system plays important roles in cancer development and treatment, and immune activation caused by chronic infection or inflammation is well-k...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.23183
更新日期:2020-07-01 00:00:00
abstract::Extracellular signal-regulated kinase 1/2 (ERK1/2) constitute a point of convergence for complex signaling events that regulate essential cellular processes, including proliferation and survival. As such, dysregulation of the ERK signaling pathway is prevalent in many cancers. In the case of BRAF-V600E mutant melanoma...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.23047
更新日期:2019-09-01 00:00:00
abstract::Although it is known that cells transformed by ras and other oncogenes show reduced gap junction function, to date there has been no investigation of the quantitative relationship between intracellular levels of ras oncoprotein and loss of cell-cell communication. Using the rat liver epithelial cell line MTR6, which c...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050307
更新日期:1992-01-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is frequently over-expressed in human cancers and is associated with tumorigenesis, and increased tumor proliferation and progression. Also found in breast tumors with high levels is B-Myb, a transcription factor whose expression is activated b...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20147
更新日期:2006-01-01 00:00:00
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
doi:10.1002/mc.22097
更新日期:2015-04-01 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