Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormalities of the EGF receptor and/or the related ERBB2 receptor occur in a significant proportion of cases of human breast cancer and are important influences in the behaviour of this tumour type. In this report we demonstrate by nucleic acid analysis and immunohistochemistry that the recently recognised third member of this gene family, ERBB3, shows a wide range of expression in breast cancer, and shows stronger immunoreactivity than that observed in normal tissue in 43 out of 195 cases (22%) of primary breast cancer. Overexpression of ERBB3 appears to result from increased levels of gene transcription since in none of the cell lines or primary cancers analysed did we find evidence of gene amplification. High expression of ERBB3 is positively associated with the presence of lymph node metastases, but there was no demonstrable relationship with patient survival in this series.
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PMID:Expression of the ERBB3 gene product in breast cancer. 133 87

Correlation between the expression of growth factor/receptor systems or the alterations of tumor suppressor genes and biological malignancy of gastric cancer was described. Overexpression of many growth factors/receptors, such as EGF, TGF alpha, EGF receptor and ERBB2, and reduction of type I receptor for TGF beta may be linked with new prognostic factors of gastric carcinomas. The expression of cripto, a novel gene of EGF family, shows a tendency to correlate with tumor staging of well differentiated gastric adenocarcinomas. p53 gene abnormalities take place in 60% of gastric carcinomas including early stage carcinoma. Loss of heterozygosity on chromosomes 1q, 7p and 7q is frequently observed in advanced gastric carcinomas of well differentiated type. Molecules which regulate tumor invasion and metastasis such as nm23, tissue inhibitor of metalloproteinase (TIMP) and endogenous galactoside-binding lectin may provide for prognostic factors of gastric cancer.
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PMID:[New prognostic factors in human gastric carcinomas]. 134 86

We illustrate the use of fluorescence in situ hybridization (FISH) for analysis of ERBB2 oncogene copy number, the level of amplification (here defined as the ratio of ERBB2 copy number to copy number of chromosome 17 centromeres), and the distribution of amplified genes in breast cancer cell lines and uncultured primary breast carcinomas. The relative ERBB2 copy number determined by FISH in 10 breast cancer cell lines correlated strongly with Southern blot results (r = 0.98) when probes for an identical reference locus were used in the two methods. Metaphase analysis of cell lines showed that amplified ERBB2 copies always occurred in intrachromosomal clusters but that the number and chromosomal location of these clusters varied among the cell lines. In interphase nuclei of primary tumors showing ERBB2 amplification (10/44), ERBB2 copies were seen as one to four clusters, also suggesting intrachromosomal localization. Regardless of the average level of amplification, all these tumors contained highly amplified cell subpopulations with at least 25, and sometimes more than 100, ERBB2 copies per cell. Tumors that did not show amplification by FISH (34/44) had an average of one to five ERBB2 copies scattered randomly in the nuclei and completely lacked cells with high copy levels. FISH results on primary tumors were concordant with slot blot results on amplification and with immunohistochemical detection of overexpression. Quantitative analysis of ERBB2 amplification by FISH may improve prognostic assessments based on the pattern of amplification and detection of heavily amplified tumor cell subpopulations.
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PMID:ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. 135 79

Overexpression and amplification of the neu (c-erbB2, ERBB2) protooncogene have been implicated in the development of aggressive human breast cancer. To directly assess the effect of mammary gland-specific expression of the neu protooncogene, transgenic mice carrying unactivated neu under the transcriptional control of the mouse mammary tumor virus promoter/enhancer were established. By contrast to the rapid tumor progression observed in several transgenic strains carrying the activated neu transgene, expression of unactivated neu in the mammary epithelium resulted in the development of focal mammary tumors after long latency. The majority of the mammary tumors analyzed expressed elevated levels of neu-encoded mRNA and protein. Overexpression of neu in the mammary tumors was also associated with elevated neu intrinsic tyrosine kinase activity and the de novo tyrosine phosphorylation of several cellular proteins. Interestingly, many of the tumor-bearing transgenic mice developed secondary metastatic tumors in the lung. These observations suggest that overexpression of the unactivated neu protein can induce metastatic disease after long latency.
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PMID:Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. 135 41

Expression of epidermal growth factor receptor (EGFR) and ERBB2 oncoprotein were studied in paraffin-embedded normal (n = 2), hyperplastic (n = 17), and malignant (n = 147) prostatic tissues by immunohistochemistry. Strong immunoreactivity was detected in the epithelial cells of all normal and hyperplastic prostates with a new EGFR antibody (Mab31G7). In prostatic carcinomas, the EGFR immunoreactivity was variable with 47% showing uniform, 39% partial, and 14% no staining. Tumors with partial or uniform EGFR immunoreactivity were locally more advanced and of higher histological grade than the EGFR-negative tumors. EGFR-positive tumors also had two to three times higher S-phase fraction, suggesting that EGFR expression conferred proliferative advantage. Patients who had either partially or uniformly EGFR-positive carcinomas had a worse 10-yr progression-free (p = 0.05), overall (p = 0.03), and prostatic carcinoma-specific (p = 0.007) survival than those with EGFR-negative carcinomas. However, according to a multivariate analysis, EGFR did not have independent prognostic value. None of the normal, hyperplastic, or malignant prostate tissues showed clearly positive ERBB2 immunoreactivity with MAb1 antibody.
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PMID:Expression of epidermal growth factor receptor and ERBB2 (HER-2/Neu) oncoprotein in prostatic carcinomas. 136 1

Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor-negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor-negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival.
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PMID:Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas. 137 10

DNA was prepared from normal tissue and 19 lung cancer cell lines. Using probes which detect restriction fragment length polymorphisms at both the topoisomerase II alpha and beta loci, heterozygosity was detected at a frequency of 0.17 and 0.37 for the alpha and beta loci, respectively. Southern blot analysis of DNA extracted from lung cancer cell lines detected amplification of both the topoisomerase II alpha and ERBB2 genes in the adenocarcinoma line Calu3. These results indicate that topoisomerase II alpha and ERBB2 may be closely linked on chromosome 17 and coamplified during adenocarcinoma progression. Since topoisomerase II is a target for several anticancer drugs, it will be of interest to study alterations to topoisomerase II genes during tumour development, as these may in part determine the response of the tumour to chemotherapy.
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PMID:Amplification of the topoisomerase II alpha gene in a non-small cell lung cancer cell line and characterisation of polymorphisms at the human topoisomerase II alpha and beta loci in normal tissue. 137 18

Genetic alterations of multiple loci that serve as markers for the induction and progression of disease have been identified in several adenocarcinomas, but not in adenocarcinoma of the prostate. To determine if similar genetic alterations occur in prostate carcinoma and could serve as markers for the extent of clinical disease, we have examined 23 predominantly moderately-differentiated, localized prostate carcinomas and one prostatic dysplasia for changes in the structure and copy number of ten selected genes. These genes include 1) those important to androgen metabolism in the prostate, the androgen receptor and steroid 5 alpha reductase genes; 2) those that map to the 10q (PLAU) and 7q (MET) chromosomal regions found deleted in some prostate carcinomas, and 3) proto-oncogenes (ERBB2, INT2, and MYC) and tumor suppressor gene loci (RB1, TP53 and D17S5) found altered in adenocarcinomas of the breast, colon and lung. Gene alterations were detected in one specimen, a lymph node metastasis from a poorly differentiated tumor. This specimen exhibited loss of heterozygosity for two loci putatively active in tumor suppression, TP53 and D17S5, on the short arm of chromosome 17. This study indicates that gross genetic alterations were not evident and could not be used as markers of tumor development in well- or moderately-differentiated, localized lesions, but that loss of the 17p region may be a useful marker for advanced carcinomas in the prostate.
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PMID:Loss of the 17p chromosomal region in a metastatic carcinoma of the prostate. 155 12

The ERBB2 proto-oncogene was studied in 539 invasive primary breast tumors and was found amplified (2- greater than 30 copies) in 19%. Amplification was correlated to most known risk factors, including; large tumor size, lymph node positivity and many tumor involved nodes, advanced stage, low patient age (less than 40 years), non-diploidy and hypertetraploidy, and most significantly (P less than 0.00001) to the absence of steroid receptors and to a high rate of proliferation (flow cytometric determined S phase fraction). ERBB2 amplification was strongly associated (P less than 0.0001) with early recurrence and death in breast cancer among node-positive patients. This connection did not, however, remain in multivariate analyses. No correlations to clinical outcome were seen among node-negative patients. Similarly, non-diploid, but not diploid, amplified tumors were particularly aggressive. Furthermore, ERBB2 amplification was associated with a high rate of proliferation and poor prognosis in steroid receptor positive, but not receptor negative tumors. In progesterone receptor positive breast cancer, amplification was an independent and with node status equally powerful (P less than 0.0001) predictor of poor survival. It is concluded that ERBB2 activity is related to an increased tumor growth rate but not directly to metastasizing ability. Its clinical relevance as a prognostic factor may be in selecting a high risk subgroup of breast cancer, in general considered as being of good prognosis.
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PMID:ERBB2 amplification in breast cancer with a high rate of proliferation. 167 31

Fifty-two primary human salivary gland tumors were analyzed for expression of the p185ERBB2 protein using immunohistochemical and immunoblotting techniques. About 63% (33/52) of the tumors expressed the ERBB2 protein. The highest expression levels were detected among the carcinomas, where 32% of the tumors showed intense membrane staining in 25-100% of the tumor cells. In benign pleomorphic adenomas, the corresponding figure was only 12%. Clinical follow-up data available for 18 of the 19 patients with carcinomas suggested an association between high ERBB2 protein levels and poor prognosis as measured by recurrence of disease and/or the appearance of metastases. These results indicate that ERBB2 activation and overexpression could be an important genetic event with possible prognostic implications in a subset of malignant salivary gland tumors.
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PMID:Expression of the ERBB2 protein in benign and malignant salivary gland tumors. 167 7


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