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)

Chinese hamster embryo (CHE) cell strains, each initiated from a separate cell stock obtained from different mothers, were transferred successively at intervals of 3 days and the changes in growth properties and karyotypes at various passages were examined. All nine cell strains proliferated at varying growth rates for 60 passages but only 2 (designated CHE A1 and CHE A2) of them expressed malignant phenotypes. The acquisition of tumorigenicity in nude mice was observed in CHE A1 and CHE A2 cells at passages 40 and 10, respectively. After 5 passages, 8 of 9 cell strains contained one or two common additional chromosomes, chromosome 3q and/or chromosome 5, although one cell strain (designated CHE A3) maintained a normal diploid karyotype for 60 passages. Trisomy of chromosome 3q was observed in all tumorigenic CHE A1 and A2 cells. One or two 3q chromosomes were detected in all tumor-derived cell lines established from tumors produced by these tumorigenic cells. DNA from tumorigenic cells and tumor-derived cell lines exhibited a high ability to transform mouse NIH3T3 cells, but we could not detect any activation of Ha-ras, Ki-ras, hst, erbB-2, mos, met or raf in any of the transformed NIH3T3 cells. These results suggest that even though cultured CHE cells can transform spontaneously, without any specific chromosome change, to immortal cells, activation of unknown oncogene(s) in addition to a specific chromosome change may be required for their malignant progression. Our results suggest that trisomy of chromosome 3q is this specific chromosome change.
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PMID:A specific chromosome change and distinctive transforming genes are necessary for malignant progression of spontaneous transformation in cultured Chinese hamster embryo cells. 762 19

Conventional cytogenetic studies of solid tumors are limited by the difficulty of culturing tumor cells, while in situ hybridization using paraffin sections of interphase cells results in too many truncated cells. To solve these problems, fluorescent in situ hybridization (FISH) technique was used on free nuclei isolated from formalin-fixed paraffin-embedded embryonal rhabdomyosarcoma (RMS) tissue using our modification of Hedley's method for isolation of nuclei. Biotinylated DNA probes for the centromeric regions of chromosomes 6, 8, 11, 12, 17, and 18, painting probes for chromosomes 8 and 11, and a cosmid probe for the HER-2/neu oncogene, were used. The centromeric probes worked well, demonstrating two copies of chromosomes 6, 17, and 18, but three copies of chromosome 11 in 52.9% of nuclei. Four copies of chromosome 8 were observed in 57.1% of nuclei and five or more in 17.1%. Chromosome 12 demonstrated 21.8% trisomy and 62.2% tetrasomy. Painting probes for chromosome 11 also worked well and matched the results of the centromeric probes, with no suggestion of structural aberration. However, the results of the painting probe for chromosome 8 yielded fluorescent areas of different sizes, suggesting that some of the extra chromosomes 8 could be deleted. The cosmid probe for the HER-2/neu oncogene also worked well, and revealed two signals in each nucleus without evidence of amplification. This study illustrates the successful use of a new technique for studying chromosomal aberration in paraffin-embedded solid tumors. The importance of this technique is that it has not been previously possible to use painting probes or cosmid probes on paraffin tissue sections. Use of this procedure will broaden the type of retrospective studies that can be performed to include detection of deletions or translocations.
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PMID:Detection of aneuploidy and possible deletion in paraffin-embedded rhabdomyosarcoma cells with FISH. 810 90

We established a novel cancer cell line (MAST) from the ascitic fluid of a metastatic infiltrating ductal carcinoma of the breast. The epithelial and neoplastic nature of the MAST cells was confirmed by ultrastructural analysis. The cell line was maintained as a monolayer with a doubling time of about 68 h, and it possessed an abnormal karyotype with a modal chromosome number of 60, a trisomy of chromosome 18 and other unidentified rearranged chromosomes. Among the markers consistently found in MAST metaphases, we noted a t(14; 14) and a very large subtelocentric, a large satellited acrocentric and a very large submetacentric chromosome with striking fluorescent bands. Immunoenzymatic assay demonstrated that the MAST cell line was positive for estrogen and progesterone receptors. The in vitro drug-sensitivity assay showed a marked resistance of the cell line to 5-fluorouracil and 4-hydroperoxycyclophosphamide and a moderate resistance to etoposide and 4'-epidoxorubicin. The molecular analysis showed a four-to sixfold amplification of the c-myc gene and no amplification or rearrangement of the int-2, c-erbB-2, c-Ha-ras, c-mos and hst-1 genes.
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PMID:A new cell line from human infiltrating ductal carcinoma of the breast: establishment and characterization. 860 77

Cervical carcinoma is a malignancy which typically occurs at the transformation zone between squamous and glandular epithelium. The vast majority falls into two histologic types, squamous cell and adenocarcinoma. In an effort to identify a subset of cervical cancer characterized by chromosome 8 trisomy, a biomarker extensively explored by this laboratory, we conducted a study of formalin-fixed, paraffin-embedded materials of cervical cancer. A total of 24 cases of cervical cancer were identified from the archives of the Rhode Island Hospital. Fluorescent in situ hybridization (FISH) using a chromosome 8 centromere enumeration probe was conducted to assess the chromosome 8 copy number in these specimens. Hybridization signals were scored among tumor cells in a blinded fashion. Tumors with >/=15% of cells with three signals were scored as trisomic. Of 24 cases studied, 23 were informative. Of the 23 informative cases, 12 (52.2%) were found to be trisomic. Eleven cases (47.8%) were disomic. The frequency of trisomy in a control chromosome 17 probe was 13.0% (3/23). Selected clinicopathologic characteristics of the tumors were also reviewed. The frequency of trisomy 8 among cases of invasive squamous cell carcinoma was 44.4% (8 of 18 tumors) and that of invasive adenocarcinoma was 80% (4 of 5 tumors). The sole tumor which was both trisomic 8 and amplified for the HER-2/neu oncogene was found to be an invasive adenocarcinoma. While the sample size in this pilot study is not large, the data obtained thus far clearly demonstrate that FISH is an appropriate technique for detecting chromosomal trisomies and that a subset of cervical cancer exists that is characterized by chromosome 8 trisomy. Further exploration of this biomarker is warranted.
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PMID:Assessment of chromosome 8 copy number in cervical cancer by fluorescent in situ hybridization. 1040 44

In a previous study, we observed a low frequency of HER-2/neu oncogene amplification in prostate cancer using fluorescent in situ hybridization (FISH). In our continued effort to identify prognostic biomarkers in prostate cancer, we analyzed 74 cases of prostate cancer to assess the presence of chromosomal trisomies in this cohort of patients. Previous results from this laboratory have implicated a role of chromosomal trisomies in various cancers. FISH using a chromosome 7 and a chromosome 8 centromere probe was utilized to study abnormal chromosome copy numbers together with data from a chromosome 17 control. The frequency of trisomy 7 was found to be 58.1% (43 of 74 informative cases), while the frequency of trisomy 8 was found to be 9.5% (7 of 74 informative cases). The frequency of cells showing chromosome 17 trisomy was 18.5% (15 of 81 cases successfully studied). While chromosome 8 trisomy did not seem to play as significant a role here as in other cancers that we studied, the results of chromosome 7 trisomy are consistent with those reported in the literature. Further exploration of selected trisomies as biomarkers in prostate cancer using a larger study sample size is warranted to establish their clinical utilities.
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PMID:Assessment of chromosomal trisomies in prostate cancer using fluorescent in situ hybridization. 1052 62

We previously conducted a study of 88 cases of prostate cancer in an attempt to identify potential prognostic biomarkers that can distinguish aggressive cases that must be treated immediately. Prostate cancer is a serious disease affecting men worldwide and compromises the quality of life of its patients. Biomarkers studied included chromosome 7 trisomy, chromosome 8 trisomy, and HER-2/neu oncogene amplification. These biomarkers were initially studied because trisomy 8 and oncogene amplification of the HER-2/neu gene have been reported in many other cancers, including those studied in this laboratory. In view of the fact that HER-2/neu amplification was not found to play a prominent role in the group of prostate cancer specimens that we studied, an exploration of other biomarkers was felt to be warranted. Thus, we began a pilot study of c-myc oncogene copy number in prostate cancer using the same protocol for fluorescent in situ hybridization and a direct-labeled SpectrumOrange LSI c-myc probe (Vysis, Inc., Downers Grove, IL) on formalin-fixed, paraffin-embedded tissue. From a total of 36 cases of prostate cancers successfully analyzed, we found 11 (31%) tumors exhibiting 3 or more positive signals for c-myc in 15% or more of the cells. Of these, only 7 tumors (19% of the total cases studied) had >/=3 signals in 20% or more of the cells. No case had >/=3 signals in 25% or more of the cells. Compared to other molecular probes tested, the c-myc signals were more faint and the quality of the preparation was less optimal than other tumor specimens that we previously studied. Based on the information available thus far, we conclude that an increased copy number in c-myc oncogene copy number was not a prominent finding in our cohort of prostate cancer patients.
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PMID:Fluorescent in situ hybridization study of c-myc oncogene copy number in prostate cancer. 1064 Apr 55

Chronic lymphocytic leukemia (CLL) is the most common leukemia in humans, with the major cytogenetic aberrations of trisomy 12 and deletion of 13q14. This study examined the influence of these aberrations on general gene replication. The study group included three subgroups: (1) 15 CLL patients, (2) 4 CLL patients with trisomy 12, (3) 3 CLL patients with deletions in 13q14. Five healthy individuals served as a control group. Monocolor fluorescence in situ hybridization (FISH) with probes for c-myc, HER-2/neu, and p53 was applied to lymphocyte nuclei for the evaluation of replication timing. Asynchronous replication (SD) rate was significantly higher in all CLL patients (P < 0.01) when compared to the control group and was even higher in the group of CLL patients with trisomy 12 and 13q14 deletion (P < 0.01). The asynchrony rate was significantly higher in cells with trisomy 12 for all three probes analyzed, compared to "healthy" cells in the same patients (P < 0.001). To conclude, in CLL patients with a chromosomal aberration such as trisomy 12 and 13q14 deletion we were able to demonstrate a high rate of asynchrony of replication. The high correlation between cells with trisomy 12 and SD pattern could reflect direct influence of the aberration on gene replication and cell cycle control.
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PMID:The influence of cytogenetic aberrations on gene replication in chronic lymphocytic leukemia patients. 1136 50

erbB-2 is amplified or overexpressed in approximately 30% of human breast cancers, and has been associated with poor prognosis and therapeutic resistance. Previous studies have suggested that erbB-2 overexpression in transgenic mice induces genomic instability; however, the patterns of genetic lesions vary with individual model systems. The development of mammary tumors in multiparous murine mammary tumor virus (MMTV)-erbB-2 transgenic mice is accelerated due to hormonal interactions which induce the overexpression of MMTV-mediated erbB-2. However, whether or not accelerated tumor development is associated with modified cytogenetic patterns remains to be determined. In this study, chromosomal changes were characterized in mammary tumor cells derived from multiparous MMTV-erbB-2 transgenic mice, and compared with tumor cells derived from control virgin mice. Immunohistochemistry and Western blotting were used to detect erbB-2 overexpression in mammary tissues. Each of the five tumors from the multiparous MMTV-erbB-2 transgenic mice was found to exhibit a marked chromosomal imbalance, compared with only one tumor with aberrant chromosomes among the five tumors from the control virgin mice. In particular, trisomy 5 and loss of the X chromosome were recurrent cytogenetic lesions in tumors from the parous mice, which is a novel pattern compared with previous studies. The elevated number of genetic lesions in tumors from parous mice, which were characterized by enhanced erbB-2 overexpression and increased receptor tyrosine kinase activation in the mammary glands, suggest a causal role for erbB-2 in the genomic instability present in these tumors. These data advance our understanding of erbB-2-mediated pathogenesis and underscore the role of cytogenetic alteration in this process.
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PMID:Trisomy chromosome 5 is a recurrent cytogenetic lesion in mammary tumors from parous MMTV-erbB-2 transgenic mice. 2284 70