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)

Five oncogenes have been implied as having a role in human breast tumorigenesis: int-2, c-erbB-2 (HER-2), c-myc, c-Ha-ras and the recessive Rb-1. As far as the function and biochemistry of these oncogenes have been studied, they act at different levels and have totally different functions in the cells. They are normally cellular genes, likely to have important functions in normal cell growth or differentiation. In the tumors their regulation or function is altered, due to a wide class of mutations. The oncogenes may cooperate to result in the malignant cell phenotype. However, different oncogenes are mutated in different tumors, so that the tumors show a variable pattern at the molecular level, underlining the individuality of these tumors already described as differences in histopathology, hormone receptor expression and clinical course. The main importance of the oncogene studies is still to reveal basic pathogenetic mechanisms. When appropriate it is important to test diagnostic or prognostic significance of the oncogene mutations.
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PMID:Oncogenes and tumor growth factors in breast cancer. A minireview. 219 33

The etiology of breast cancer is thought to involve a complex interplay of various factors, among them: genetic alterations. Multiple studies have been made to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, some of these alterations involve implication of proto-oncogenes (c-myc, c-erbB-2 and int-2) that have been shown to contribute to tumorigenesis by using the transgenic mouse model. Loss of heterozygoty represents the other important type of abnormalities that has been frequently observed in breast tumor DNAs; these specific genic deletions could inactivate or remove suppressor genes. In some studies, specific alterations have been associated with some clinical parameters, but have led to numerous controversies. Larger studies would be necessary to confirm some alterations as useful prognostic factors of the post-surgical course of the disease.
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PMID:[Cancer of the breast. Genetic alterations and prognostic factors]. 223 89

MCF-7 human breast cancer cells are estrogen dependent for maximal in vitro growth and for tumor formation in nude mice, thus providing a useful model system to study mammary tumorigenesis. A clone of MCF-7 cells transfected with the v-rasH oncogene has been shown to form tumors in the absence of estradiol [Kasid et al., 1985, Science (Wash. DC), 228:725-728]. To extend this observation to more clones of v-rasH-expressing MCF-7 cells and to examine the effects of rasH mutation, we transfected MCF-7 cells with a construct encoding the human c-rasH protooncogene protein product and with three isogenic constructs encoding proteins containing point mutations: arg-12, thr-59, and arg-12 + thr-59 (v-rasH). We isolated several cell lines which produced levels of c-rasH and v-rasH p21 at 30- to 50-fold the levels of controls. We also isolated several cell lines producing the various mutants p21s. All of the transfected cell lines were estrogen-responsive for cell growth. Transfected cells containing high levels of rasH p21 had correspondingly high levels of growth in an anchorage-independent growth assay. Tumorigenesis studies in nude mice, however, showed that some, but not all of the cell lines expressing v-rasH, formed tumors in the absence of estradiol. Tumor formation did not correlate with the level of rasH p21 expression in these cell lines. No tumor formation in the absence of estradiol was observed for cell lines expressing single-mutated or unmutated forms of rasH.
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PMID:Growth properties and tumorigenesis of MCF-7 cells transfected with isogenic mutants of rasH. 240 19

A serious effort has been made to identify and characterize mutations that frequently occur during the evolution of primary human breast cancer. Some of these mutations involve amplification of protooncogenes (c-myc, c-erbB-2, and int-2) that have been shown to contribute to experimentally induced breast cancer in mouse model systems. Tumor development in mice containing the c-myc or c-erbB-2 transgene suggests that the cellular and developmental contexts in which the genes are expressed define their relative contribution to tumorigenesis. Homozygous deletions or loss of heterozygosity (LOH) represent another type of mutation that has been frequently observed on four chromosomes (1q, 3p, 11p, and 13q) in tumor DNA. They are thought to unmask recessive mutations (LOH) that inactivate or remove (homozygous deletion) suppressor genes that regulate normal cell proliferation. Attempts to determine whether specific mutations are associated with certain clinical parameters have led to the controversial hypothesis that some mutations may be useful prognostic indicators of the post-surgical course of the disease. The current results underscore the necessity for much larger, better control studies to unambiguously define the potential of such mutations as clinical markers.
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PMID:Genetic alterations in primary breast cancer. 266 53

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

The expression of epidermal growth factor (EGF) receptor in brain tumours of glial origin was studied at the protein, mRNA and genomic levels. Four out of 10 glioblastomas that overexpress EGF receptor also have gene amplification. The amplified genes appear to be rearranged, generating an aberrant mRNA in at least one of these tumours. Such receptor defects may be relevant to tumorigenesis of human glioblastomas.
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PMID:Amplification and overexpression of the EGF receptor gene in primary human glioblastomas. 301 20

Using the adjacent histologically normal tissues obtained from the same patients as controls, six human lung tumors were studied for the activities of epidermal growth factor (EGF) receptor binding, and receptor autophosphorylation. There was a 1.2- to 2.8-fold increase in EGF receptor activities in lung tumors due to an increase in the number of receptors without changes in their affinity. The increase had no direct correlation with the degree of differentiation or the type of lung tumors. The elevated expression of EGF receptor may be one of the characteristics in lung tumors. Epidermal growth factor and its receptor also may play a role in the regulatory mechanisms during tumorigenesis.
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PMID:Expression of epidermal growth factor receptors in human lung tumors. 348 15

Cell kinetics is a predictive parameter of breast-cancer aggressiveness, and mutations occurring in mammary tumorigenesis may favor uncontrolled cell proliferation. In this study, cell kinetics, clinico-pathological characteristics and genetic alterations at the int-2, bcl-1, c-myc, c-erbB-2, and DF3 loci were analyzed and correlated in 54 primary breast carcinomas. The occurrence of mutations at more than one locus was also studied. Tumor-proliferative activity was evaluated by determination of the thymidine labeling index (TLI). Amplification (AMP) of int-2 was observed in 11.2%, of bcl-1 in 9.4%, of c-myc in 5.7% and of c-erbB-2 in 8.6% of the carcinomas. Loss of heterozygosity (LOH) at the DF3 locus was detected in 13.9% of the tumors. Genetic alterations demonstrated a significant association with patient's age and high TLI values. AMP and LOH+AMP did not appear to be statistically related to histotype, histological grade, tumor size or lymph-node status. Alone, allele loss at the DF-3 locus was not significantly associated with any of the clinico-pathological characteristics studied. Alterations at more than one locus, including int-2/bcl-1, int-2/c-myc, int-2/bcl-1/c-erbB-2, and c-myc/DF3, were detected in 11.1% of the tumors. Multiple mutations were found only in less differentiated tumors, which included the 2 cases from the youngest patients of the series.
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PMID:High cell kinetics is associated with amplification of the int-2, bcl-1, myc and erbB-2 proto-oncogenes and loss of heterozygosity at the DF3 locus in primary breast cancers. 770 20

We describe a differential screening method for cDNA libraries which used a combination of subtracted and PCR-amplified cDNA probes, and which can be applied to the selection of genes expressed in multiple tissues. This technique was used to identify genes commonly overexpressed in breast and basal cell carcinomas. These represent stromally dependent, invasive tumors with and without metastatic capacity. Thus, this screening sought to identify genes involved in the early stages of tumor progression. We identified a total of 16 genes, including c-erbB-2 and tissue inhibitor of metalloproteinases 3 whose products have been implicated in tumorigenesis or invasion. We also identified a novel sequence (D52) showing little homology with others described in any species, which maps to the human chromosomal band 8q21. In situ RNA hybridizations of breast carcinoma sections indicated that the D52 gene was expressed in cancer cells, whereas other genes identified in the differential screening were expressed in fibroblastic or inflammatory cells within the tumor stroma. Thus, the procedure developed in this study selected genes expressed in a diversity of cell types, indicating its potential usefulness in other systems.
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PMID:A screening method to identify genes commonly overexpressed in carcinomas and the identification of a novel complementary DNA sequence. 779 18

The c-erbB-2 (HER-2/neu) proto-oncogenes is important in oncogenesis and for determination of prognosis in a number of human malignancies. DNA (Southern) hybridization and immunoblotting (Western) techniques are most commonly utilized for determining amplification status and protein expression of this proto-oncogene, respectively. These extraction techniques are often time-consuming, costly, and subject to variability depending on the histological characteristics of the tumor. Paraffin-immunohistochemistry (P-IHC), on the other hand, is time and cost-effective. In addition, this technique may offer enhanced sensitivity and specificity over extraction techniques due to the in situ nature of analysis. In data presented here, 67 cases of human mammary carcinoma were concomitantly assessed for c-erbB-2 gene copy number and oncoprotein expression by dilutional DNA hybridization and P-IHC, respectively. In 64 (95.5%) of 67 cases, high level expression was associated with gene amplification, whereas no detectable expression was associated with a normal diploid gene copy number. In two of the three discrepant cases, P-IHC predicted amplification not corroborated by Southern analysis. In these cases, tumor mass was limited by the intraductal component of the lesion or by an abundance of stromal elements within the specimen. We conclude that P-IHC offers a favorable alternative to Southern analysis in the assessment of c-erbB-2 gene copy number of this oncoprotein in human mammary carcinoma. Furthermore, immunohistochemistry may prove superior to either extraction technique in specimens with limited tumor mass, such as biopsy materials, stroma-rich tumors, or early stage lesions such as intraductal carcinoma.
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PMID:Assessment of c-erbB-2 amplification by immunohistochemistry in paraffin-embedded breast cancer. 790 29


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