Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on EGF receptor (EGFR) phosphorylation and the expression of mRNAs for oncogenes, growth factors, their receptors and metalloproteinase genes by MKN-28 gastric carcinoma cells which express EGF, TGF-alpha and EGFR genes. Both EGF and TGF-alpha stimulated EGFR phosphorylation, EGF and TGF-alpha induced FOS, MYC and ERBB-2 oncogene expression. Interestingly, EGF increased the expression of mRNAs for TGF-alpha and EGFR. On the other hand, TGF-alpha increased TGF-alpha mRNA but decreased the expression of mRNAs for EGFR and TGF-beta. Furthermore, mRNAs for interstitial collagenase, stromelysin and procollagen type I genes were also enhanced after treatment with EGF and TGF-alpha. These results indicate that EGF and TGF-alpha successively evoke cascade phenomena which favor tumor progression, invasion and extracellular matrix formation, acting as autocrine growth regulators for gastric carcinomas.
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PMID:Induction of growth factor-receptor and metalloproteinase genes by epidermal growth factor and/or transforming growth factor-alpha in human gastric carcinoma cell line MKN-28. 216 68

DNA amplification seems to be particularly frequent in human breast tumours and has been associated with cancer evolution and aggressiveness. Recent data indicate that new events should be added to the list, such as the amplifications at chromosome 20q13 or the MDM2 gene. The present work aimed at determining the incidence and clinicopathological signification of these amplifications in a large series of breast and ovarian tumours. We tested 1371 breast and 179 ovarian tumours by Southern blotting and observed amplification of 20q13 in 5.4% breast and 2.8% ovarian carcinomas, whereas MDM2 was found amplified in 5.3% and 3.8% of breast and ovarian tumours respectively. MDM2 RNA expression levels were analysed in a subset of 57 breast tumours and overexpression was observed in 4/57 (7%) of the tumours. Elevated expression levels coincided with amplification of the gene. In breast cancer, 20q13 and MDM2 amplifications seem to define subsets of aggressive tumours. Indeed, 20q13 was correlated to axillary nodal involvement and occurred preferentially in younger patients (< 50 years). Furthermore, 20q13 correlated, as did MDM2 amplification, to aneuploidy. In parallel, we had also tested our tumour DNAs for amplification of CCND1, ERBB-2 and MYC, which made it possible to test for correlations with 20q13 or MDM2 amplifications. Whereas 20q13 showed a very strong correlation to CCND1 amplification, that of MDM2 was prevalent in MYC-amplified tumours. Interestingly, 20q13 and MDM2 amplifications showed some degree of correlation to each other, which may possibly be owing to the fact that both events occurred preferentially in aneuploid tumours. In ovarian cancer, no statistically significant correlation was observed. However, 20q13 amplification occurred preferentially in stage 3 tumours and MDM2 was correlated to ERBB-2 amplification. This may suggest that in ovarian tumours also, 20q13 and MDM2 amplifications occur in late or aggressive cancers.
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PMID:DNA amplifications at 20q13 and MDM2 define distinct subsets of evolved breast and ovarian tumours. 898 Apr 1

The bladder cancer cell line BK-10 was established from a grade III-IV transitional cell carcinoma (TCC). BK-10 is near-tetraploid (+/-4n) and consists of two subclones with 20-25 structural aberrations. Here we report the cytogenetic analysis of BK-10 by G-banding, spectral karyotyping (SKY), and FISH. SKY refers to the hybridization of 24 differentially labeled chromosome painting probes and the simultaneous visualization of all human chromosomes using spectral imaging. SKY enabled us to confirm 12 markers in BK-10 previously described by G-banding, redefine 11 aberrations, and detect 4 hidden chromosomal rearrangements, 2 of which had been identified as normal or deleted copies of chromosome 20 and 1 as a normal chromosome 3. Twenty out of 21 translocations identified were unbalanced. FISH analysis of BK-10 using chromosome arm-specific paints, centromere probes, and oncogene/tumor suppressor gene-specific probes revealed a deletion of CDKN2A (p16) in all copies of chromosome 9, a low-level amplification of MYC (five copies), and loss of one copy of TP53; detected the presence of the Y chromosome in a hidden translocation; and detected four copies of ERBB-2. A probe set for BCR and ABL verified breakpoints for all translocations involving chromosomes 9 and 22. A new karyotype presentation, "SKY-gram," is introduced by combining data from G-banding, SKY, and FISH analysis. This study demonstrates the approach of combining molecular cytogenetic techniques to characterize fully the multiple complex chromosomal rearrangements found in the bladder cancer cell line BK-10, and to refine the chromosomal breakpoints for all translocations.
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PMID:Molecular cytogenetic analysis of the bladder carcinoma cell line BK-10 by spectral karyotyping. 1022 40

The profile of genetic alterations in four breast carcinoma cell lines, SK-BR-3, BT-474, MDA-MB361 and ZR-75-1 was examined by comparative genomic hybridization, G-band karyotyping, reverse chromosome painting and fluorescence in situ hybridization of single-copy genes. These lines are aneuploid with complex structural rearrangements and have DNA copy-number imbalances involving multiple sites that include amplification of ERBB-2 and MYC proto-oncogenes which are implicated in breast cancer pathogenesis. A novel site of high level amplification was mapped on chromosome 15. All lines were tumorigenic in nude mice, however, the latency and the incidence of tumor formation varied; SK-BR-3 and MDA-MB361 produced tumors in a shorter time and had a higher total number of genomic imbalances compared to BT-474 and ZR-75-1 cells. Tumor cell behavior in vivo was not reflected by the rate of in vitro cell proliferation. Underrepresentation on the long arm of chromosome 18 was the sole alteration that correlated with an increased tumorigenicity. Chromosome 18q is rich in tumor suppressor genes and its loss is prevalent in primary node-positive breast tumors. Cell lines with monoclonal populations preserve the genetic characteristics of the primary tumor and their use may facilitate the detection of specific alterations associated with breast cancer progression.
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PMID:Profile of genetic alterations and tumorigenicity of human breast cancer cells. 1063 63

The aim of this study was to evaluate the expression profile of proteins involved in growing of human non-small cell lung cancer (NSCLC) in athymic nude mice. The expressions of 20 gene products in primary NSCLC of 170 patients were analyzed and the proteins were correlated with the transplantability of the carcinomas in nude mice. There was no relationship between xenotransplantability of human non-small cell lung cancer in nude mice and histology, stage or lymph node involvement. Of the analyzed proliferative factors PCNA, cyclin A, cyclin D, cdk2, cdk4 and cell cycle phases only cyclin D, cdk4 and the cell cycle phases were up-regulated in growing carcinomas. There was also a correlation between the apoptotic indices and the take rate in nude mice. Concerning microvessel density and angiogenic factors only VEGF showed a relation to xenotransplantability. Of the proto-oncogenes and suppressor gene products N-RAS, P53, FOS and JUN revealed a relationship to the take rate of NSCLC, while such a relationship was not found with MYC, ERBB-1 and ERBB-2. In a second step, a hierarchical cluster analysis was carried out. The resulting clusters were correlated with the take rate of the carcinomas in nude mice. The expression of JUN, N-RAS, FOS, cyclin D, and cdk4 were significantly different in both groups with non- overlapping confidence intervals. Thus, the up-regulation of the proteins JUN, N-RAS, FOS, cyclin D and cdk4 predicts the growth of NSCLC in nude mice.
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PMID:Expression profile of proteins involved in the xenotransplantability of non-small cell lung cancers into athymic nude mice. 1178 7

Prognostic factors related to the recurrence and progression of superficial primary bladder cancers were analyzed by Cox's proportional hazards regression model. We followed 75 patients (stage Ta, 49 cases; T1, 26 cases; grade G1, 42 cases; G2, 29 cases; G3, 4 cases) after transurethral resection for 10 to 74 months (median 38 months). The antibodies reactive with the products of oncogenes [anti-c-myc oncoprotein (MYC-1); anti-c-erbB-2 oncoprotein], tumor suppressor gene [anti-p53 mutant protein (BP53-12)], growth factor receptor [anti-transferrin receptor (HBT-2)], proliferation [anti-proliferatioe nuclear antigen (Ki-67)], and malignant transformation (B1.4) were used for immunohistochemical staining. The reactivities of mAb B1.4, HBT2, and BP53-12 were significantly increased according to the grade, and those of mAb Ki-67, MYC-1, and c-erbB-2 were not. The reactivities of all antibodies were not significantly different between stages Ta and T1. As prognostic factors, stage, grade, tumor number, urinary cytology, and reactivities of the above six antibodies were used for the analysis. Urinary cytology, multifocality, and the reactivity of mAb Ki-67 showed a relative but significant high risk for recurrence, and the reactivities of mAb HBT2, mAb B1.4, and mAb Ki-67 showed a significant high risk for progression in the multivariate analysis. These results suggest that mAb B1.4 may be useful as a new prognostic factor for the progression of superficial bladder cancer.
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PMID:A multivariate analysis of prognostic factors related to recurrence and progression of superficial bladder cancer. 2122 61

Aberrant epidermal growth factor (EGF) receptor (EGFR) signaling contributes to neoplastic initiation and progression in lung. Mutated EGFR has become as an important therapeutic target in lung cancer, whereas targeted treatment is not available for wild-type EGFR or its ligands. In this study, we found that heparin-binding (HB)-EGF, a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells. We observed that, upon HB-EGF induction, CITED4 was induced through a signal transducer and activator of transcription 3 (STAT3)-dependent pathway, regulating cell proliferation. CITED4 interacted with MYC and potentiated MYC-mediated transactivation of the CCND1 promoter, leading to cell cycle progression. Correlation analysis revealed that HB-EGF and CITED4 were significantly positively associated in primary lung tumors, and expression of HB-EGF predicted a poor survival outcome in patients. In vitro and in vivo experiments revealed that pharmacological inhibition of HB-EGF with CRM197 significantly attenuated tumor cell growth. Thus, CITED4 functions as a molecular switch in HB-EGF-induced growth control, and HB-EGF provides a novel therapeutic target for lung cancer intervention.
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PMID:A targetable HB-EGF-CITED4 axis controls oncogenesis in lung cancer. 2809 74

Globally, breast cancer is the second leading cause of cancer-related mortality among women, with approximately 1.4 million new cases diagnosed annually. Associated genetic perturbations are emerging in the face of intense scientific enquiry, facilitating its classification, prognostication and treatment. RNAi, utilizing siRNA, is a powerful treatment strategy to silence disease-causing genes. However, therapeutic siRNA instability and poor cellular uptake have limited its clinical application, necessitating the use of nanocarriers. In this review, we highlight the RNAi mechanism, HER-2/neu and MYC as breast cancer gene targets, and nonviral nanocarriers as potentially safe and efficient delivery systems.
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PMID:HER-2/neu and MYC gene silencing in breast cancer: therapeutic potential and advancement in nonviral nanocarrier systems. 3251 63