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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alterations in the structure and/or expression of oncogenes have been examined to comprehend better the relationship between metastasis and oncogenes. There are reports that amplification and overexpression of N-myc (human neuroblastoma) and erbB-2 (human breast cancer) are closely related to malignant progression. On the other hand, DNA transfer experiments have also been done to assess involvement of oncogenes in metastasis. The active ras oncogenes, which are frequently used, show that transfer of the ras oncogenes endow and/or enhance the metastatic potential of the recipient cells. In addition to the phenomenological studies to determine whether an oncogene alters metastatic potential, increasing attention has been directed to possible phenotypic changes relating to metastasis and affected by oncogenes. It has been clarified that transfer of a certain oncogene, such as ras and fos, alters the expression of biomolecules, for example, metalloproteinases responsible for invasion, autocrine motility factors and cytoskeletal proteins related to cell motility, receptors of fibronectin for cell attachment, and histocompatibility antigens, such as H-2K and H2-D. While further characterization of the biomolecular changes induced by the oncogenes has to be done, the mechanisms of alteration in the expression and function of biomolecules directly involved in the metastatic potential also should be paid attention.
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PMID:[Cancer metastasis and oncogenes]. 267 90

Functional characterization of oncogene products that induce cellular transformation has progressed rapidly in recent years. However, less is known about the mechanism(s) by which the transformed cells may escape destruction by host immune defenses and form tumors. A recently described oncogene that has an important association with aggressive human breast carcinoma is "HER2," for human epidermal growth factor receptor 2. The oncogene has also been called NGL and human c-erbB-2 (ERBB2). In this paper we show that amplification of HER2 oncogene expression can induce resistance of NIH 3T3 cells to the cytotoxic effects of recombinant tumor necrosis factor alpha (rTNF-alpha) or macrophages. Resistance is accompanied by an increased dissociation constant for rTNF-alpha binding to high-affinity receptors on the HER2-transformed NIH 3T3 cells. The resistance phenotype is independent of transformation since NIH 3T3 cells transformed by the activated human homologue of the Harvey-ras oncogene (HRAS) retain high-affinity binding sites for rTNF-alpha as well as sensitivity to its cytotoxic effects. These results suggest that HER2 may potentiate tumorigenesis by inducing tumor cell resistance to host defense mechanisms.
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PMID:Amplified expression of the HER2/ERBB2 oncogene induces resistance to tumor necrosis factor alpha in NIH 3T3 cells. 289 23

Regulation of transcription of members of the ras gene family undoubtably plays an important role in controlling cellular growth. Examination of this level of regulation requires identification of the promoter regions of the ras proto-oncogenes. Four major transcriptional start sites were detected in the human Harvey ras 1 proto-oncogene. The promoter region contains neither a TATA box nor a CAAT box in their characteristic upstream positions, has an extremely high G+C content (80 percent), and contains multiple GC boxes including seven CCGCCC repeats and three repeats of the inverted complement, GGGCGG. This region has strong promoter activity when placed upstream from the chloramphenicol acetyl transferase gene and transfected into monkey CV1 cells. In these ways the Harvey ras 1 proto-oncogene promoter resembles the promoter of the gene encoding the epidermal growth factor (EGF) receptor. The similarity between the two proto-oncogene promoters may be relevant to the mechanism by which the expression of such "growth control" genes is regulated.
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PMID:Promoter region of the human Harvey ras proto-oncogene: similarity to the EGF receptor proto-oncogene promoter. 299 83

The methylation state of cellular oncogenes (c-oncs) and epidermal growth factor (EGF) receptor gene from human liver tissues was examined by means of restriction endonuclease analysis. c-myc and EGF receptor gene from hepatocellular carcinoma and fetal liver were substantially hypomethylated in comparison with those genes from normal liver, while the extents of methylation of c-mos and c-Ki-ras genes were the same among these tissues. It can be speculated that the specific hypomethylation of c-myc and EGF receptor genes may be associated with the development of hepatocellular carcinoma.
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PMID:Hypomethylation of c-myc and epidermal growth factor receptor genes in human hepatocellular carcinoma and fetal liver. 300 5

The promoter of the human c-K-ras gene has been characterized by deletion mutagenesis in concert with stable and transient expression gene transfer experiments. The transcription initiation sites were determined by S1 mapping and RNase A protection experiments. The c-K-ras promoter region is rich in G + C, lacks TATA and CCAAT boxes and contains sequence similarities with other house-keeping genes such as the dihydrofolate reductase (DHFR) and the epidermal growth factor (EGF) receptor genes. The promoter of the c-K-ras gene consists of multiple elements and initiation of transcription occurs at multiple sites. A 54 bp DNA fragment immediately upstream from the 5' end untranslated exon controls the position of many of the transcription initiation sites and direct sufficient transcription for transformation of NIH3T3 cells. However, these sequences can be replaced by other upstream sequences which are required for optimal gene expression. In addition, sequences overlapping with the 5' end untranslated exon and therefore downstream from the major transcription initiation sites are important (although not sufficient) for transcription because their deletion greatly impairs the promoter activity of the upstream elements.
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PMID:Characterization of the human c-K-ras gene promoter. 306 87

It is generally believed that estrogen may act either as an initiator or as a promoter in carcinogenesis of human breast cancer. This estrogenic action is generally dependent on the estrogen receptor. In the human estrogen receptor, cDNA has a homology to V-erb-A oncogene. Experiments using MCF-7 human breast cancer cells were carried out to study the regulatory effect of estrogen and antiestrogen on RNA activities of oncogenes, estrogen receptor gene, and epidermal growth factor (EGF) receptor gene. The effect of estradiol on activation of estrogen and EGF receptor genes and myc, ras, and fos oncogenes was positive in relation to the concentrations of supplemented estradiol. In addition, the effects of antiestrogen (tamoxifen) were investigated. Tamoxifen suppressed MCF-7 cell growth, and spot hybridization of the RNA of MCF-7 cells revealed that RNA activities of estrogen and EGF receptor genes and myc, ras, and fos oncogenes were suppressed by tamoxifen. These results suggest that the three oncogenes and two receptor genes are partly regulated by estrogen and antiestrogen (tamoxifen) in MCF-7 human breast cancer cells. This regulatory system may have a role in carcinogenesis and in the treatment of human breast cancer.
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PMID:Regulation of human estrogen receptor gene, epidermal growth factor receptor gene, and oncogenes by estrogen and antiestrogen in MCF-7 breast cancer cells. 324 19

DNAs from fifty-three primary breast cancers were hybridized with 16 different proto-oncogene or oncogene probes. Abnormalities of one or more of five proto-oncogenes were found in fifty-eight percent of tumors at the time of mastectomy. Amplification of c-myc and c-erbB-2, and allelic deletions of c-ras-Ha and c-myb were the most common abnormalities. The presence of altered proto-oncogenes correlated with clinical stage of the cancers. Fifteen of 43 evaluable tumors of stages I to III recurred, and four of five evaluable stage IV tumors progressed within 16 to 24 months of surgery. All but one of the cancers that recurred or progressed had detectably altered proto-oncogenes (P less than .001). Analysis of proto-oncogenes may have prognostic value in breast cancer.
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PMID:Proto-oncogene abnormalities in human breast cancer: correlations with anatomic features and clinical course of disease. 347 61

To determine the frequency and clinical significance of oncogene abnormalities in colon cancer, deoxyribonucleic acids from 45 colon carcinomas and 15 benign adenomas were hybridized with 14 different protooncogene probes. Abnormalities of oncogenes were found in 22% of cancers at the time of resection. Amplification of c-myc or c-erbB-2 and allelic deletion of c-ras-Ha or c-myb were the most frequent abnormalities. The presence of altered oncogenes did not correlate with Dukes' stage, tumor progression, or patient survival after resection. One adenoma had an allelic deletion of the c-myb oncogene which was not seen in either the normal colon or an adjacent carcinoma. These data indicate that the spectrum of altered protooncogenes in colon carcinoma is similar to that of other adenocarcinomas, and that unstable oncogenes can be found before overt malignancy develops.
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PMID:Protooncogene abnormalities in colon cancers and adenomatous polyps. 355 13

Twenty-seven primary non-small cell (NSC) lung cancers were analyzed for alterations of protooncogenes by DNA hybridization techniques. Abnormalities were found in 56% of tumors including ten of 16 adenocarcinomas, three of nine squamous cell cancers and two of two larger cell cancers. Five protooncogenes were found to be commonly altered in tumors at frequencies between 12% and 60%. These were c-myc, c-myb, c-ras-Ha, c-erbB-1 and c-erb-B-2. Alterations in c-erbB-1 and c-erbB-2 correlated with histologic type of tumor and were more common in advanced cancers. Allelic deletions of c-ras-Ha or c-myb were frequently observed in primary tumors which recurred or progressed after surgery (five of six). Analysis of protooncogenes may provide insights into the pathogenesis of lung cancer and may aid in predicting clinical behavior.
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PMID:Abnormalities of protooncogenes in non-small cell lung cancer. Correlations with tumor type and clinical characteristics. 367 3

Although mutations in ras genes are thought to be important for the development of about 20% of human tumors, almost nothing is known about the way in which these mutations lead to cellular transformation. The known biochemical properties of the 21-kilodalton ras proteins suggest that they may behave as G proteins, regulating the proliferation of cells in response to growth factor stimulation of a receptor. Although the putative receptor(s) has not been identified, several lines of evidence, in particular the fact that rodent cell lines containing ras oncogenes produce transforming growth factor alpha, have suggested that the epidermal growth factor (EGF) receptor is involved in ras transformation. Here we show that murine fibroblasts with no EGF receptors can be transformed to a completely malignant phenotype with a mutated ras gene. It appears, therefore, that the EGF receptor is not required for ras-mediated transformation of these cells.
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PMID:Malignant transformation of murine fibroblasts by a human c-Ha-ras-1 oncogene does not require a functional epidermal growth factor receptor. 379 84


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