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)

Abnormalities of some oncogenes, antioncogenes and losses of heterozygosity (LOH) of chromosome 11p, 17p, and 17q in colorectal carcinomas (CC) was studied. Amplification of ERBB-1/HER-1 oncogene was detected in 2 of 56 cases; ERBB-2/HER-2- in 4 of 62. There was a lack of evidence for C-MYC oncogene amplification (67 cases). LOH of chromosome 11p (HRAS-1 probe) was found in 2 of 37 informative (heterozygous) cases; such events were not accompanied by point mutations in "hot" codons (12th or 61st) in the remaining allele. Prevalence of A3 and A4 alleles of HRAS-1 oncogene (68 cases) as compared to healthy donors was noted. RB-1 (41 cases) and p53 (62 cases) suppressor genes did not show any alterations in Southern-blot analysis. LOH of chromosome 17p (YNZ-22 probe) was found in 15 of 26 heterozygous CC; 17q (THH-59 probe)--in 4 of 16. Analysis of 175th codon of p53 gene revealed only one case of mutation in 35 CC studied. Finally, we were able to detect genetic alterations in 23 of 40 (58%) CC, that were studied on each parameter using Southern-blot. We failed to find any correlation between various molecular abnormalities or clinical characteristics. The data obtained are in disagreement with the view concerning frequent involvement of p53 antioncogene in chromosome 17p deletions.
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PMID:[Complex characteristics of the alterations of oncogenes HER-2/ERBB-2, HER-1/ERBB-1, HRAS-1, C-MYC and antioncogenes p53, RB1, as well as deletions of loci of chromosome 17 in colon carcinoma]. 147 Jan 78

The changes in the expressions of the protooncogene protein c-Myc, its dimerization partner Max and the competitive inhibitors Mad1 and Mxi1 during the terminal differentiation of chondrocytes in vivo were investigated by immunocytochemistry. The four immunoreactivity patterns in the epiphyseal plate cartilage of growing rats, as they appeared under the light microscope, showed differences in protein expression level and intracellular distribution, with the chondrocyte developmental stage. c-Myc immunoreactivity was intense and mainly in the nuclei of proliferative chondrocytes. It decreased in the nuclei of mature chondrocytes and appeared in the cytoplasm. c-Myc immunoreactivity increased in the fully-differentiated hypertrophic chondrocytes. Immunoreactivity of the c-Myc dimerization partner Max was mainly in the nucleus of proliferative chondrocytes and decreased as the chondrocytes matured. Mad1 immunoreactivity was also concentrated in the nucleus of proliferative chondrocytes, but was mainly in the cytoplasm of mature chondrocytes and almost lost from the hypertrophic chondrocytes. Lastly, there was Mxi1 immunoreactivity in the nucleus and cytoplasm of proliferative, mature and early hypertrophic chondrocytes and the cytoplasm staining was more sustained than in the nucleus. There was little labeling in late hypertrophic chondrocytes. The electron microscope pictures corroborated these findings and showed the subcellular distributions of the immunolabelings. The gold particles reflecting Mad1 frequently formed patches and those for Mxi1 appeared to accumulate within the mitochondria of all chondrocytes. The variations in immuno-patterns and intracellular distributions suggest that each protooncogene protein has specific roles in the functional changes in the chondrocytes at each step of their terminal differentiation.
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PMID:Expression and subcellular localization of the Myc superfamily proteins: c-Myc, Max, Mad1 and Mxi1 in the epiphyseal plate cartilage chondrocytes of growing rats. 913 Jun 2

Some molecular genetic and biochemical features of malignant breast tumors were studied in females living in North-Western Russia. ERBB-2 oncogene amplification frequently (25%) occurred and was associated with poor outcomes. The frequency of C-MYC extra copies was lower (3%) than that in Europe and the USA. Deletions at chromosome 17p were associated with ERBB-2 amplification and the lack of nodal involvement. Moreover, it is concluded that endogenous hormonal and metabolic parameters, as well their changes due to some environmental factors (smoking), plays a great role in the modification both of breast cancer risk and autocrine-paracrine relationships in the very tumor tissue and of the hormone sensitivity of the latter.
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PMID:[Molecular biological and biochemical features of breast cancer]. 951 35

Hereditary ovarian cancers associated with germline mutations in either BRCA1 or BRCA2 were studied to determine whether somatic mutation of the P53 gene is required for BRCA-linked ovarian tumorigenesis and further, whether the spectrum of additional somatic molecular genetic alterations present in these tumors differs from that known to exist in sporadic ovarian cancers. Forty tumors, 29 linked to BRCA1 and 11 linked to BRCA2, were examined for mutational alterations in P53, K-RAS, ERBB-2, C-MYC, and AKT2. The presence of a P53 mutation in 80% of these cancers indicates that P53 mutation is common but not required for BRCA-linked ovarian tumorigenesis; notably, a significantly higher proportion of the P53 mutations in BRCA2-linked cancers were deletions or insertions compared with the more typical spectrum of missense mutations seen in BRCA1-linked cancers. Additionally, BRCA-linked ovarian carcinomas seem to develop through a unique pathway of tumorigenesis that does not involve mutation of K-RAS or amplification of ERBB-2, C-MYC, or AKT2.
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PMID:Molecular genetic characterization of BRCA1- and BRCA2-linked hereditary ovarian cancers. 969 40

Limited information is currently available on chromosomal abnormalities in esophageal adenocarcinoma and associated premalignant lesions. In this study, numeric changes affecting chromosomes 4, 6, 7, 8, 9, 10, 11, 12, 17, 18, X, and Y were analyzed by using fluorescence in situ hybridization (FISH) with chromosome-specific centromere DNA probes in 12 esophageal adenocarcinomas. In addition, TP53 overexpression, measured by immunohistochemistry, and amplification of HER-2/neu and C-MYC, detected by FISH, were analyzed within the same tumors. The most common numeric abnormalities detected were gains of chromosomes 12 (8 cases), 6 (7 cases), 7 (7 cases), and 11 (6 cases). The total number of abnormal chromosomes varied from 0 to 10, with an average of 4.6 per case. Overexpression of TP53 was present in 9 of 12 cases. No correlation was noted between the degree of aneusomy and TP53 overexpression. In contrast, HER-2/neu amplification was present in two cases, both with large numbers of aneusomic chromosomes. Amplification of C-MYC was detected in only one case that had a moderate number of numeric abnormalities. In a subset of cases in which premalignant lesions were examined, aneusomy was found to be an early change, frequently present in both Barrett's esophagus and dysplastic regions. In contrast, gene amplification and TP53 overexpression were restricted to more advanced areas of dysplasia and malignancy. Screening larger cohorts of patients with Barrett's esophagus or dysplasia for numeric abnormalities of chromosomes 6, 7, 11, and 12 may determine whether any of these abnormalities are predictive markers of progression to malignancy.
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PMID:Interphase cytogenetics of esophageal adenocarcinoma and precursor lesions. 977 3

We looked for the protooncogene protein, c-Myc, its dimerization partner, Max, and the repressors of its transactivation activity, Mad1 and Mxi1, in the epiphyseal-plate cartilage matrix of growing rats by immunocytochemistry in the electron microscope. c-Myc and Mxi1 immunoreactivities were found in the calcifying areas of the cartilage matrix only. There was no immunolabeling in response to anti-Max or anti-Mad1 antibodies. Mxi1 immunoreactivity was mainly in the early calcifying areas, in the calcification front and ahead of it, whereas c-Myc immunoreactivity was essentially in the incompletely calcified regions of the matrix. The two immunolabelings occurred mainly over the large type II collagen fibrils of the cartilage matrix and over the thin filaments connecting them. c-Myc and Mxi1 immunoreactivities were rarely found along the dark cristallites. There was no immunolabeling associated with the matrix vesicles, or in their immediate surroundings. The data suggest that the protooncogene proteins, c-Myc and Mxi1, could be implicated in the calcification involving type II collagen fibrils of the epiphyseal-plate cartilage. The absence of Max immunoreactivity from the calcifying cartilage matrix raises the question of whether there are other c-Myc- and Mxi1-dimerization partners.
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PMID:c-Myc and Mxi1 immunoreactivities in the calcifying areas of the epiphyseal-plate cartilage matrix of growing rats. 1037 97

We have examined whether the extended life span of cells induced by Bcl-2 in T(1) ductal breast carcinomas might favor the acquisition and accumulation of genetic alterations that induce lymph node metastases. We analyzed the expression of c-Myc, c-erbB-2 and epidermal growth factor receptor by immuno-histochemistry in a group of 142 T(1) (<2 cm) ductal breast carcinomas embedded in paraffin, previously studied for p53 mutation and Bcl-2 over-expression. We also measured the apoptotic status and estimated the excess risk (pOR) for lymph node metastasis according to the number of accumulated oncogene alterations and Bcl-2 and p53 expression. The linear relationship between number of oncogene alterations and presence of lymph node metastasis was statistically significant in Bcl-2-positive tumors (trend test, p = 0.03), p53-mutated tumors (trend test, p = 0.08) and tumors with loss of apoptosis (trend test, p = 0.08). Very large associations (pOR > 12) between the number of oncogene alterations and lymph node metastasis were observed among Bcl-2-positive tumors that showed increased loss of apoptosis (trend test, p = 0.03). Furthermore, in p53-negative tumors, a strong linear association was found between the number of oncogene alterations and risk of lymph node metastasis among Bcl-2-positive tumors (trend test, p = 0.03). In human T(1) ductal breast carcinoma, over-expression of Bcl-2 along with loss of apoptosis might render breast cancer cells susceptible to the acquisition of additional genetic lesions related to disease progression among p53-negative tumors. Thus, in breast cancer, there are at least 2 pathways to progression: Bcl-2- and p53-dependent mechanisms.
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PMID:Bcl-2 with loss of apoptosis allows accumulation of genetic alterations: a pathway to metastatic progression in human breast cancer. 1075 91

The coding region determinant-binding protein (CRD-BP) binds in vitro to c-myc mRNA and is thought to stabilize the mRNA and increase c-Myc protein abundance. The CRD-BP gene has 15 exons and 14 introns, is single-copy, and is located on chromosome 11 in mice and 17 in humans, close to HER-2/neu. The CRD-BP gene is moderately amplified in 12 of 40 human breast cancers; it is highly amplified in 2 others (14.4 and 20 copies). Despite their proximity, CRD-BP and HER-2/neu genes can be amplified independently. Amplification of a gene that might up-regulate c-Myc abundance could accelerate breast cancer.
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PMID:Amplification in human breast cancer of a gene encoding a c-myc mRNA-binding protein. 1085 Apr 8

Gene amplification is an important mechanism of oncogene activation in breast and other cancers. Characterization of amplified regions of the genome in breast cancer has led to the identification of important oncogenes including erbB-2/HER-2, C-MYC, and fibroblast growth factor receptor (FGFR) 2. Chromosome 8p11-p12 is amplified in 10-15% of human breast cancers. The putative oncogene FGFR1 localizes to this region; however, we show evidence that FGFR inhibition fails to slow growth of three breast cancer cell lines with 8p11-p12 amplification. We present a detailed analysis of this amplicon in three human breast cancer cell lines using comparative genomic hybridization, traditional Southern and Northern analysis, and chromosome 8 cDNA microarray expression profiling. This study has identified new candidate oncogenes within the 8p11-p12 region, supporting the hypothesis that genes other than FGFR1 may contribute to oncogenesis in breast cancers with proximal 8p amplification.
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PMID:Genomic and expression analysis of the 8p11-12 amplicon in human breast cancer cell lines. 1472 6

It has been previously demonstrated that human ovarian cancer cells express FSH receptor (FSHR). However, whether FSHR plays a role in ovarian cancer development is still ambiguous. To investigate the role of FSHR in tumor progression, we overexpressed the receptor in SV40 Tag immortalized ovarian surface epithelium (OSE) cell lines (IOSE-80PC, a postcrisis line, and IOSE-398), which are preneoplastic and nontumorigenic. We compared the expression levels of several selected oncogenes in nontransfected (80PC), vector-transfected (80PCV), FSHR-transfected IOSE (80PCF) cells, and established ovarian cancer cell lines (OVCAR-3 and SKOV-3). Significantly increased protein levels of epithelial growth factor receptor, HER-2/neu, and c-Myc, but not K-Ras, were observed in FSHR-overexpressing 80PCF cells when compared with 80PCV cells. Constitutive phosphorylation of ERK1/2 was augmented in 80PCF cells, whereas phosphorylation of the other MAPK including p38 and Jun N-terminal kinase was unchanged. Considerable constitutive phosphorylation of ERK1/2 was also observed in OVCAR-3 and SKOV-3 cell lines when compared with 80PCV. More importantly, 80PCF cells grew more rapidly than 80PC and 80PCV cells. In conclusion, we have demonstrated that FSHR was highly expressed in OVCAR-3 and 80PCF cells transfected with FSHR overexpression vector. The 80PCF cell line showed increased levels of epithelial growth factor receptor, HER-2/neu, and c-myc and constitutive activation of ERK1/2. The rate of proliferation of the 80PCF cells was increased, compared with control cell lines. These results suggest that the overexpression of FSHR may be associated with enhanced levels of potential oncogenic pathways and increased proliferation in preneoplastic ovarian surface epithelial cells.
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PMID:Overexpression of follicle-stimulating hormone receptor activates oncogenic pathways in preneoplastic ovarian surface epithelial cells. 1553 6


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