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)

Abnormally expressed oncogenes are implicated in neoplastic transformation. We have investigated a series of endocrine tumours using immunocytochemistry as a first screening tool to detect oncogene expression. Paraffin sections of 44 pulmonary small cell carcinomas, 15 pulmonary atypical carcinoids, 12 bronchial carcinoids, 28 medullary thyroid carcinomas, 27 phaeochromocytomas, and 17 insulinomas were immunostained with antibodies to c-erbB-2, c-myc, L-myc, and N-myc. Diffuse immunoreactivity was detectable for c-erbB-2 in 8 out of 44 (18 per cent) pulmonary small cell carcinomas, 3 out of 15 (20 per cent) pulmonary atypical carcinoids, and 6 out of 27 (22 per cent) phaeochromocytomas; for c-myc in 18 out of 44 (41 per cent) pulmonary small cell carcinomas and 5 out of 15 (33 per cent) pulmonary atypical carcinoids; for N-myc in 6 out of 28 (21 per cent) medullary thyroid carcinomas; and for L-myc in 4 out of 27 (15 per cent) phaeochromocytomas. There was considerable intratumoral and intertumoral heterogeneity and, in each tumour group, no relationship was found between tumour pattern, mitotic index, and oncoprotein immunoreactivity. These results suggest that oncogene products are present in a proportion of endocrine tumours, and that specific oncoproteins seem to be related to tumour type but not to other histopathological findings. Thus, oncoprotein detection may be a useful tool for identifying subsets of endocrine tumours that are not otherwise recognizable morphologically.
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PMID:Oncoprotein immunoreactivity in human endocrine tumours. 167 55

Amplification of the c-erbB-2 protooncogene has been associated with a poor prognosis in human breast and ovarian cancers. Our study was undertaken to examine whether amplification, rearrangement, or overexpression of c-erbB-2 and other protooncogenes was frequently observed in epithelial ovarian cancers. c-erbB-2 was expressed in 87% of 22 ovarian cancers analyzed, but expression was significantly increased in only one of the 22 tumor specimens. In this case elevated c-erbB-2 expression was associated with dramatic amplification of the gene. In another tumor a 3.8 kb EcoRI fragment was found, in addition to the usual 4.4 and 6.0 kb fragments; this is consistent with a possible gene rearrangement or a restriction fragment length polymorphism. To place these results in perspective, expression of several other protooncogenes has been examined in ovarian carcinomas. The c-fos, c-myc, n-myc, c-fms, and c-Ha-ras protooncogenes were expressed in different fractions of tumors, but expression of l-myc, c-erbB, c-myb, c-sis, and c-mos was not detectable. Aside from c-erbB-2, neither amplification nor rearrangement was observed among the other protooncogenes studied. Expression of c-erbB-2, c-fms, c-myc, n-myc, c-fos, and c-Ha-ras deserves further evaluation as a prognostic factor in ovarian cancer.
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PMID:Expression and amplification of the HER-2/neu (c-erbB-2) protooncogene in epithelial ovarian tumors and cell lines. 167 63

The development of human lung cancer may require multiple genetic deletions affecting a number of chromosomes, e.g., 1, 3, 11, 13, and 17. These genetic aberrations may induce the activation of proto-oncogenes (c-jun, ras, c-raf1) and the loss of tumor suppressor genes (p53). Some of the activated proto-oncogenes and tumor suppressor genes are more selectively expressed or absent in small-cell lung cancer (L-myc, c-myb, c-scr, Rb gene) or non-small-cell lung cancer (c-erbB-2, c-sis, c-fes). These genes may thus be of importance for selection of differentiation pathway. The c-myc oncogene is frequently amplified in small-cell lung cancer cell lines in a much higher frequency than in vivo. This indicates that c-myc seems to be related to tumor progression and a relatively late event in the lung cancer development. The uncontrolled production of multiple growth factors has been identified in human lung cancer cell lines. These factors can promote and inhibit the proliferation via paracrine and autocrine loops via specific receptors. The products from some of the activated proto-oncogenes (c-sis, c-erbB-2) are sequences homologous to a certain growth factor (PDGF) and a receptor (EGF) identified in lung cancer. The production and action of these growth factors may be of major importance for further activation of proto-oncogenes via intracellular signal transduction and specific oncogenic activation leading to further tumor progression.
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PMID:Gene amplification in human lung cancer. The myc family genes and other proto-oncogenes and growth factor genes. 217 59

To examine a potential contribution of protooncogene abnormalities other than point-mutational activation of the K-ras protooncogene in the classification of non-small cell lung cancer, amplification of cellular protooncogenes was studied in 47 lung tumour specimens obtained at thoracotomy and in four lung tumour cell lines. The primary tumours included 21 adenocarcinomas, nine large-cell carcinomas, 13 epidermoid carcinomas, one carcinoid and three metastases of primaries outside the lung. The copy numbers per haploid genome of 11 protooncogenes in every tumour sample were determined: H-ras, K-ras, N-ras, c-myc, N-myc, L-myc, erbB, mos, myb, ncu (erbB-2) and ral amplifications. The c-myc gene was amplified 5-7-fold in two adenocarcinomas, the H-ras gene 3 5-fold in one adenocarcinoma, while the K-ras and the neu gene were amplified in lung metastases from a colorectal and a breast cancer primary respectively. None of the tumours with an amplified protooncogene simultaneously harboured a mutationally activated K-ras gene. We conclude that amplification of the investigated protooncogenes is a rare event in non-small cell lung cancer. In view of the two c-myc amplifications detected, a systematic study of c-myc expression levels in non-small cell lung cancers appears worthwhile.
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PMID:Cellular protoonocogenes are infrequently amplified in untreated non-small cell lung cancer. 254 15

The possible existence of amplification or rearrangement of protooncogenes was examined in more than 100 surgical specimens of human lung carcinoma. Protooncogenes were amplified in 28% of the carcinomas. About 90% of the amplified genes were of the myc, ras, or erbB family. Of the myc family genes, myc was amplified in 14 of 137 tumors and L-myc in four of 108 tumors, but N-myc was not amplified. A high frequency of amplification of myc was observed in squamous cell carcinomas (seven of 37) and of L-myc in small cell carcinomas (two of six). Of the ras family genes, K-ras-2 was amplified in six of the 137 tumors and N-ras in two of the 137 tumors, but no amplification of H-ras-1 was detected. Seven of the eight cases of amplified ras genes were in advanced pathological stages. Of the erbB family genes, erbB-1 (epidermal growth factor receptor) was amplified in 10 of 114 tumors and erbB-2 (HER-2/neu) in one of 51 tumors. Amplifications of the myc, ras, and erbB family genes might be one of the crucial DNA abnormalities involved in the development of human lung carcinomas.
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PMID:Amplification of protooncogenes in surgical specimens of human lung carcinomas. 257 14

Benign breast disease (BBD) is a heterogeneous group of benign breast problems that has been associated with breast cancer risk by several investigators. Genetic alterations have been described in breast carcinomas under the headings of loss of heterozygosity (1p, 3p, 7q, 11p, 17p, 17 and 18q), mutations (p53, c-H-ras-1), and/or gene amplifications (c-myc, int-2/FGF3, and c-erbB-2/neu). In an attempt to determine whether these genetic alterations might also be involved in the development of BBD, we have analyzed such alterations in 50 BBD lesions. The histological types of samples studied were: 37 fibroadenomas; 8 benign phyllode tumors; and 5 fibrocytic diseases. Cellular DNA was extracted from tissues and from corresponding blood leukocytes according to standard techniques, digested with appropriate restriction endonucleases, and analyzed by Southern blot. The following are informative cases found in a total number of patients analyzed for each locus: 13 of 26 for L-myc (1p); 9 of 23 for THRB (3p); 11 of 29 for met (7q); 27 of 50 for c-H-ras-1 (11p); 3 of 13 for TP53 (17p); 14 of 50 for D17S30 (17p); 20 of 33 for D17S4 (17q); and 13 of 33 for D18S5 (18q). No loss of heterozygosity was detected at any of the examined loci. Alternatively, none of the 50 BBD cases displayed an amplification of the three genes tested (c-myc, int-2/FGF3, and c-erbB-2/neu). Our results show that molecular alterations, which are more frequently involved in malignant breast carcinomas, do not occur in BBD lesions. These results indicate that these molecular alterations could constitute late events in the pathogenesis of breast carcinomas.
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PMID:Benign breast disease: absence of genetic alterations at several loci implicated in breast cancer malignancy. 767 Dec 54

DNA content analysis using flow cytometry and amplification of c-myc, L-myc, and c-erbB-2 oncogenes in 143 cases of resected lung cancer were analyzed using the same specimen, and we examined the correlation with prognosis of DNA content and amplification of oncogenes. There were 54 DNA diploid cases (38%), 81 DNA aneuploid cases (57%) and 8 DNA multiploid cases. Analysis of oncogene amplification revealed 22 cases of c-myc, 4 cases of L-myc, and 22 cases of c-erbB-2. In curatively resected cases, the 5-year survival rate was 65% in 31 DNA diploid cases, and 36% in 40 DNA aneuploid cases. There was a statistically significant difference between the two groups (p < 0.02). However, in non-curatively resected cases, the 5-year survival rate was 11% in 23 DNA diploid cases, and 33% in 49 DNA aneuploid cases. There were no statistically significant differences among these groups. The correlation between DNA content and amplification of oncogenes was as follows. In DNA diploid cases, there were 4 cases of c-myc, and 6 cases of c-erbB-2. In DNA aneuploid cases, there were 15 cases of c-myc, 4 cases of L-myc, and 15 cases of c-erbB-2. In DNA multiploid cases, there were 3 cases of c-myc, and 1 cases of c-erbB-2. Amplification of oncogenes was seen more frequently in DNA aneuploid and multiploid cases than in DNA diploid cases. In 71 curative resected cases, the 5-year survival rate for amplified cases of c-myc (10 cases) was 0%, and that of cases with no amplification was 61% (no statistically significant difference). The 5-year survival rate for amplified cases of c-erbB-2 (10 cases) was 40%, against 52% for cases with no amplification. DNA content analysis using flow cytometry was more convenient than analysis of amplification of oncogenes, and reflects the prognosis of resected lung cancer better than oncogenes. There was no relation between DNA content and gene amplification.
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PMID:[Correlation between DNA content and amplification of oncogenes (c-myc, L-myc, c-erbB-2) and correlation with prognosis in 143 cases of resected lung cancer]. 809

Pleomorphic adenoma of the lung is a rare neoplasm. Here we describe the first report on oncogenes and tumor suppressor genes in metastasizing pleomorphic adenoma of the lung. A 48-year-old Japanese woman presented with metastasizing pleomorphic adenoma in which both the primary lung tumor and metastatic lesions were composed of benign pleomorphic structures. The mechanism of the metastatic potential was examined by analyzing known oncogenes and tumor suppressor genes by DNA blot analysis and immunohistochemistry. No rearrangements amplifications or overexpressions of oncogenes, bcl-2, c-erbB-2, c-myc, L-myc, N-myc, Ha-ras and Ki-ras were found. In addition, immunohistochemical studies showed no aberrance in expressions of the tumor suppressor gene products, RB, p16 and p53 in the tumor. Some unknown mechanism(s) seems to be responsible for the aggressiveness of this metastasizing pleomorphic adenoma. This mechanism must be elucidated by studies on further case of this rare tumor.
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PMID:A case of pleomorphic adenoma of the lung with multiple distant metastases--observations on its oncogene and tumor suppressor gene expression. 967 59

A new human cancer cell line was established from a metastatic lesion of a small cell lung carcinoma (SCLC-R1) and maintained in continuous culture with a doubling time of 62 h. The SCLC-R1 line, whose ultrastructural features are presented, showed a diploid DNA content, a translocation involving chromosome 16 [t(16;?)(q24;?)] and noticeable deletions in the FHIT (fragile histidine triad) region in the short arm of chromosome 3 [del(3)(p14)] and in the telomeric region of the short arm of chromosome 12 [del(12)(p13)]. The involvement of 12p in metastatic small cell lung cancer is reported here for the first time. No amplification or rearrangements were evident in the c-myc, L-myc, N-myc, int-2, c-erbB-2, H-ras, K-ras, c-mos, and hst-1 genes by Southern blot analysis. Wild-type p53, RB, K-ras and H-ras genes were evident by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. The neuron specific enolase (NSE) level was much higher in the cell line's cytosol than in the patient's serum and the cell line also had high expression of chromogranin A and cytokeratin 19. SCLC-R1 cells were sensitive to cisplatin, carboplatin and doxorubicin. The clinical history of the patient from whom the cell line was derived is reported. The characteristics of this new cell line indicate it to be a useful experimental model to investigate lung cancer biology and anticancer drug response.
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PMID:Chromosomal alterations, biological features and in vitro chemosensitivity of SCLC-R1, a new cell line from human metastatic small cell lung carcinoma. 971 81

The analysis of oncogene expression may provide insights into the pathogenesis of small cell lung cancer (SCLC) and may help to predict clinical behavior. The expression of 8 oncogenes (c-myc, N-myc, L-myc, Ha-ras, Ki-ras, N-ras, erbB-2, v-sis) was evaluated in small cell lung cancer (SCLC) xenografts of tumor samples, recentlly transplanted, taken from 17 different patients. Eight of these 17 SCLC lines expressed the L-myc oncogene and 2 SCLC lines expressed the c-myc oncogene. One SCLC line (SCLC-63M) simultaneously expressed the L-myc and c-myc oncogenes. All SCLC lines examined had almost similar high RNA levels of the Ki-ras oncogene, while the expression of Ha- and N-ras oncogenes was not always observed. The N-myc and v-sis oncogenes were expressed in only one tumor and at a very weak level, and no transcript of the erbB-2 oncogene was observed in any of our 17 SCLC lines. These results indicate that oncogene expression in SCLC lines is heterogeneous, with the exception of the Ki-ras oncogene which is constantly overexpressed.
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PMID:Heterogeneous expression of oncogenes in small-cell lung-cancer xenografts. 2157 1


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