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)

Immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA distribution patterns were assessed in 119 formalin-fixed paraffin-embedded surgical specimens of human mammary carcinomas in situ (CIS). The series consisted of 107 ductal carcinomas in situ (DCIS), 9 lobular carcinomas in situ, and 3 cases of Paget's disease of the nipple. Nuclear DNA distribution patterns were assessed by image cytometric analysis of histopathologically identified cell nuclei. Fifty-one of 107 (48%) DCIS were immunoreactive for c-erbB-2, whereas specific cell membrane staining was absent in lobular carcinomas in situ. The neoplastic cell nuclei of 46 CIS (39%) were of DNA diploid type, and 73 CIS (61%) contained aneuploid nuclear DNA. Among various histopathologic subtypes of DCIS, significant differences in c-erbB-2 immunoreactivity and nuclear ploidy were observed. DCIS of the comedo type most often were c-erbB-2 positive and exhibited aneuploid nuclear DNA histograms. DCIS of micropapillary type was the second most frequently reactive c-erbB-2 expression, and aneuploidy were less common in solid, cribriform, and papillary DCIS. The results of the current study indicate that immunohistochemical expression of the c-erbB-2 proto-oncogene product is closely related to the histopathologic subtype and the nuclear DNA content of mammary CIS. Examples of CIS that are c-erbB-2 immunoreactive and DNA aneuploid seem to have a significantly higher risk for the subsequent development of infiltrating mammary carcinoma.
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PMID:Immunohistochemical c-erbB-2 protooncogene expression and nuclear DNA content in human mammary carcinoma in situ. 137 18

Alterations in cellular biochemistry which are associated with the development of resistance to cytotoxic peptides, such as tumor necrosis factor (TNF), may also be responsible for changes in the response of cells to cytotoxic agents. Culturing ME-180 cervical carcinoma cells in the presence of escalating concentrations of TNF resulted in the development of an ME-180 cell variant (ME-180R) resistant to TNF but expressing a 3-5-fold increased sensitivity to cisplatin (CDDP) when measured following continuous exposure (low doses) or short-term incubation with CDDP (high doses) and clonogenic analysis. Cellular platinum uptake, efflux, and nuclear platinum content as well as the extent of DNA platination were examined and found to be identical in both ME-180 parental and ME-180R cell lines. Although ME-180R cells showed a relatively higher glutathione content than ME-180 parental cells, the effect of buthionine sulfoximine on the cellular sensitivity to CDDP and glutathione S-transferase activities of both cell lines were almost identical, suggesting that glutathione content or its metabolism did not appear to play a major role in differential CDDP cytotoxicity. Unscheduled DNA synthesis following exposure to CDDP was more inducible in ME-180 parental cells than in CDDP-sensitive ME-180R cells. Alkaline elution studies of cross-linked DNA in CDDP-treated ME-180 cells suggested that accumulation of DNA adducts reached maximal levels 10-15 h after CDDP treatment and was similar in both TNF-resistant and parental cells. Within 24 h after CDDP exposure, the extent of DNA cross-linking was markedly reduced in parental cells but remained elevated in the CDDP-sensitive ME-180R cell line. To examine the proposed regulatory role of phosphorylation in CDDP and TNF-mediated cytotoxicity, epidermal growth factor (EGF) receptor tyrosine kinase activity was measured in both TNF-resistant and parental ME-180 cells. Analysis of cell lysates demonstrated a 3-4-fold higher EGF receptor tyrosine kinase activity in ME-180R cells when compared to the parental population which correlated with increased expression of EGF receptor protein by immunoblot analysis. Based upon colony-forming assays, EGF treatment of ME-180 parental cells resulted in an increased sensitivity to CDDP (similar to ME-180R cells) and 3-fold stimulation of EGF receptor tyrosine kinase activity. Taken together, these results suggest that TNF resistance in ME-180 cervical carcinoma cells correlates with both increased EGF receptor expression and enhanced CDDP cytotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Resistance of human cervical carcinoma cells to tumor necrosis factor correlates with their increased sensitivity to cisplatin: evidence of a role for DNA repair and epidermal growth factor receptor. 138 Aug 90

Increased expression of epidermal growth factor (EGF) receptor has been recorded in many types of human tumors and has been associated with reduced survival in ovarian carcinoma. The purpose of this study was to examine the immunocytochemical distribution of the EGF receptor in normal ovaries (n = 30) and in ovarian tumors (n = 126). Staining was observed in two normal ovaries, in the granulosa cells of a developing follicle, and in surface epithelium. Forty-seven of 103 malignant common epithelial tumors were immunopositive. Staining was usually focal, always confined to the neoplastic epithelium, and showed a cytoplasmic distribution. There was a slight trend for increased EGF receptor expression in more advanced common epithelial malignancies, but this was not statistically significant. No correlation between immunoreactivity and histological subtype or grade of tumor was seen. A few other tumors were also examined: one each of Brenner tumor, mature teratoma, mature teratoma with squamous carcinoma, borderline serous tumor and fibroma; all were immunopositive.
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PMID:Expression of epidermal growth factor receptor in normal ovary and in ovarian tumors. 139 32

ICR 12, one of a panel of rat monoclonal antibodies recognizing the external domain of the human c-erb B2 proto-oncogene product, (Styles, 1990) was chosen as a candidate for radiolabeling with 124I for positron emission tomography of selected patients with breast cancer. By using N-bromosuccinimide (NBS), optimal labeling conditions were established using 125I. The labeling efficiency was determined using instant thin-layer chromatography (ITLC) and gel filtration (HPLC). The antibody was then labeled with the positron emitter 124I, and a labeling efficiency of 96% and immunoreactivity of 80%-90% was obtained. The product was stable, with less than 5% of the radiolabel being eluted after six days storage in plasma at 37 degrees C. Immunolocalization studies were performed in athymic mice bearing human breast carcinoma xenografts overexpressing the c-erb B2 gene product using as controls 125I labeled isotype-matched rat antibody, and antigen-negative tumors. Good uptake of 124I-labeled ICR12 was obtained in c-erb B2 expressing tumors (up to 12% injected dose per gram at intervals up to 120 hr), with localization indices of 3.4-6.2. Tumor xenografts of 6 mm diameter were successfully imaged with high resolution at 24, 48 and 120 hr using the RMH/ICR MUP-PET camera. We suggest that 124I-labeled ICR12 is a suitable agent to image and quantify immunolocalization in patients whose tumors overexpress the c-erb B2 proto-oncogene product.
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PMID:c-erbB2 protein overexpression in breast cancer as a target for PET using iodine-124-labeled monoclonal antibodies. 146 May 9

Scatter factor (SF) was first identified as a fibroblast-derived protein which disperses (i.e., "scatters") cohesive colonies of epithelium. SF-like proteins were found in human smooth muscle cell conditioned medium, amniotic fluid, and placental tissue. SFs markedly stimulate migration of epithelial, carcinoma, and vascular endothelial cell types at picomolar concentrations. Hepatocyte growth factors (HGFs) were originally described as platelet- and serum-derived proteins which stimulate hepatocyte DNA synthesis. Partial amino acid sequence data for mouse and human SFs indicate significant homology with HGFs. We used biological, biochemical, and immunological assays to evaluate and compare the activities, properties, and mechanisms of action of mouse SF, human SF (fibroblast or placenta derived), and recombinant human HGF (hrHGF). We report the following findings: (a) mouse SF exhibits species-related differences in biological activities relative to the human factors; (b) human SF and hrHGF show significant overlap in biological activities (i.e., hrHGF stimulates motility of multiple normal and carcinoma cell types, whereas human SF stimulates DNA synthesis in several normal cell types); (c) the three factors contain common antigenic determinants; and (d) all three proteins stimulate rapid phosphorylation of tyrosine residues on the c-met protooncogene protein product (the putative receptor for HGF) and on another protein with Mr 110,000. A few biological and immunological differences between human SFs and hrHGF were observed. These may reflect minor variations in amino acid sequence or posttranslational modification related to the sources of the factors. Taken as a whole, our findings suggest that by structural, functional, immunological, and mechanistic criteria, human SF and human HGF are essentially identical.
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PMID:Scatter factor and hepatocyte growth factor: activities, properties, and mechanism. 153 87

We previously reported that the expression on the primary tumour of the antigen CaMBr8 was related to a short survival, attributable either to higher tumour aggressiveness or a poor response to oophorectomy. To further verify the CaMBr8 prognostic value, we analysed retrospectively 862 breast cancer patients with a 19 year follow-up. In this series, CaMBr8 expression was found to be associated to some negative prognostic factors (premenopausal status, lymphnode invasion, a high number of mitosis and HER-2/neu oncoprotein expression), but had no influence on the patients' survival. Direct association with a poor prognosis was only evident in patients with lobular or mixed breast carcinoma, which however represent only a small fraction of the total breast cancers. Another possibility was that CaMBr8 could identify a subgroup of patients which did not respond to hormone therapy. To verify this hypothesis we evaluated on a second series of 116 patients the relationship between CaMBr8 expression and hormone-receptor levels. A negative association emerged which was also observed in vitro in the human breast cancer line MCF-7 treated with Sodium Butyrate, a differentiation inducer, which reduced hormone-receptor levels and increased CaMBr8 expression. In conclusion, the longer survival of CaMBr8 negative tumour patients observed in the initial study, was probably related to a better response to oophorectomy, due to the hormone-receptor level of their tumours.
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PMID:Study of the biological and prognostic significance of the antigen CaMBr8 on breast carcinoma. 155 5

The c-erbB-2 protooncogene encodes a possible growth factor receptor. This gene has been studied as to whether it can be regarded as a prognostic indicator in human breast carcinoma. As amplification and overexpression of the gene have been reported in several adenocarcinomas, 24 specimens of human gastric cancers were examined by immunohistochemical staining (24 cases), by Southern blotting (23/24) and by Northern blotting (16/24). Amplification of the gene was detected in two moderately differentiated tubular adenocarcinomas (8.7%), and overexpression of c-erbB-2 mRNA was detected in three moderately differentiated tubular adenocarcinomas (18.8%). By immunohistochemical staining of paraffin-embedded tissues using a polyclonal antibody to c-erbB-2 gene products, the cell membrane was stained positively in three cases of gastric cancers which overexpressed c-erbB-2 mRNA. Peritoneal metastases were found in six gastric cancers, including two moderately differentiated tubular adenocarcinomas in which amplification of c-erbB-2 occurred. These results suggest that amplification and overexpression of c-erbB-2 may be correlated with metastases in differentiated adenocarcinoma of the stomach.
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PMID:Amplification and overexpression of the c-erbB-2 protooncogene in human gastric cancer. 157 21

We examined tyrosine kinase activity of epidermal growth factor (EGF) receptor in a total of 34 human gastric carcinomas as well as in non-neoplastic gastric mucosa from the same patients. EGF receptor kinase activity of the carcinoma tissues and the non-neoplastic mucosa were 1.28 +/- 1.00 (Mean +/- S.E.) and 0.16 +/- 0.04 respectively, if the EGF receptor kinase activity of human placenta is 10. Twenty-one (62%) carcinoma tissues showed higher EGF receptor kinase activity than corresponding non-neoplastic mucosa, while in 6 cases (18%) the kinase activity was higher in the non-neoplastic mucosa than in the tumor tissues. No obvious correlation was observed between the increased kinase activity in the tumors and histological type or tumor staging. One tumor showed extremely high receptor kinase activity with ERBB gene amplification. This tumor showed strong immunoreactivity to EGF itself.
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PMID:Tyrosine kinase activity of epidermal growth factor receptor in human gastric carcinomas. 159 97

Prognostic predictors for node-negative breast carcinoma have not been clearly established. Immunostaining with Ki-67 antibody was performed on frozen sections of histologically proved node-negative breast carcinomas from 42 patients to examine its prognostic value and its association with other clinicopathologic and biochemical parameters, i.e., patient age and tumor size, histologic type, nuclear grade, mitotic rate, presence of vascular or lymphatic invasion, DNA ploidy, percentage of cells in S-phase, estrogen content, and c-erbB-2 amplification. Thirty-seven of the 42 tumors showed immunoreactivity with Ki-67 antibody in 1% to 55% of the tumor cells. A strongly significant correlation was observed between Ki-67 staining percentage and, respectively, nuclear grade, age, and mitotic rate. Nuclear grade 1 (the most anaplastic) tumors showed a significantly higher median percentage of cells stained (median, 14; range, 3 to 40) compared with nuclear grade 3 tumors (median, 0.5; range, 0 to 8). Thirteen patients developed recurrence; six of them died of disease. On univariate analysis, both 5-year disease-free and overall survivals were strongly associated with percentage of cells stained with Ki-67 antibody. Our results suggest that Ki-67 immunostaining correlates well with nuclear grade and clinical outcome in node-negative breast carcinoma. Because of small sample size analyzed in this study we were unable to do multivariate analysis. Therefore, further studies with larger number of cases are needed to determine whether tumor proliferative activity determined by Ki-67 immunostaining is an independent prognostic parameter or it merely reflects histopathologic features such as nuclear grade or mitotic activity.
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PMID:Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. 164 33

From a single spontaneous feline mammary carcinoma, two subpopulations of epithelial tumor cells have been isolated. The variant cells were established as cell lines designated K248C and K248P. DNA ploidy analysis showed that the two cell lines represented cell populations already present in the original tumor. Chromosome analysis confirmed the feline origin of K248C and K248P and demonstrated that in addition to unique marker chromosomes characteristic for each cell line, both cell lines had several marker chromosomes in common. These data suggest that the two cell populations arose from a hypothetical single ancestor which diverged during tumor progression. The K248C and K248P cell lines differed from one another with respect to their tumorigenicity in athymic mice and epidermal growth factor (EGF) receptor content. The K248C cells were highly tumorigenic as indicated by a short latency period and high take rate. The K248P cells were poorly tumorigenic. Southern blot analysis revealed that the K248C cells contained an amplified EGF receptor gene that was accompanied by elevated levels of EGF receptor RNA and protein. The K248C cells were growth inhibited in vitro at EGF concentrations that stimulated growth of K248P cells. The amplification of the EGF receptor gene could be detected only in DNA derived from K248C cells at high passage numbers and not in DNA derived from the original tumor and K248C cells at low passage numbers. These data suggest that amplification of the EGF receptor gene occurred during establishment of the K248C cell line.
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PMID:Isolation of two distinct epithelial cell lines from a single feline mammary carcinoma with different tumorigenic potential in nude mice and expressing different levels of epidermal growth factor receptors. 164 97


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