Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression and coexpression of EGFR, c-erbB-2 and c-erbB-3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables. Generally, gastric cancer patients showed a higher incidence of EGFR, c-erbB-2 and d-erbB-3 overexpression than the group with chronic gastritis (81% and 43%; 38% and 45%; 35% and 20%, respectively), however, statistically significant differences were found only for EGFR expression (p = 0.01). No association between immunoreactivity of all growth factor receptors and the histopathological structure of gastric cancer was observed. EGFR and c-erbB-3 proteins were detected more frequently in patients with III/IV than in I/II of TNM stages, while c-erbB-2 overexpression was higher in I/II vs. III/IV stages. In chronic gastritis with intestinal metaplasia and or coexisting carcinoma lesions, a higher frequency of the expression of studied proteins was observed in comparison with chronic gastritis without those alternations; however, these differences were statistically insignificant. The percentage of positive cases with coexpression of two proteins was comparable in gastric cancer and chronic gastritis (33% and 35%) but the simultaneous expression of all three receptors was evident only in gastric cancer (19%). Our results indicate that at least one or two members of EGFR related receptors could appear in the early stages of gastric tumorigenesis. The enhancement of c-erbB-2 and c-erbB-3 reactivity seems to cooperate with EGFR activation in the gastric cancer development. Our results indicate the promotional rather than direct transformational role for EGFR supergene family in gastric carcinogenesis.
 ...
PMID:Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. 970 36

The erb type 1 tyrosine kinase receptors are important for mediating proliferation and differentiation, and aberrant activation may contribute to tumour development and progression. They comprise epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3, and c-erbB-4. There are overlaps and differences in the cellular distribution of the four receptors, which is of significance since they can form heterodimers that give differing responses to different ligands. The different distributions could be of particular importance in cancer if therapeutic modalities are identified to inhibit or stimulate the different ligands.
 ...
PMID:The erbB/HER type 1 tyrosine kinase receptor family. 977 75

Nuclear retinoid and membrane c-erbB receptors participate in signal transduction systems that control mammary epithelial cell proliferation and differentiation. Recently, we demonstrated that c-erbB receptor activation stimulates retinoic acid receptor-alpha expression. We now report that retinoids reduce SK-BR-3 breast cancer cell growth by inhibiting the cell cycle and by inducing apoptosis. This is accompanied with reduced c-erbB expression as determined by FACS, Western, Northern, RT-PCR, and reporter assays. All-trans (ATRA) and 9-cis retinoic acid (9cRA) reduce c-erbB-1 protein to 50-100%, c-erbB-2 to 20-30%, and c-erbB-3 to 10-50% of control, depending on the concentration, respectively, without influencing the tyrosine phosphorylation status. Down-regulation of c-erbB-2 and -3 was seen at all levels analyzed, whereas c-erbB-1 mRNA remained unchanged. Retinoic acid-mediated down-regulation of growth and c-erbB-2 and -3 expression was also seen in MCF-7 cells. We conclude that retinoic acids are efficient repressors of c-erbB-2 and -3 gene expression, whereas c-erbB-1 is not markedly affected.
 ...
PMID:Retinoids control the expression of c-erbB receptors in breast cancer cells. 979 Oct 9

The type 1 family of growth factor receptors, which consist of the epidermal growth factor receptor, c-erbB-2, c-erbB-3, and c-erbB-4, are expressed in normal breast ductal epithelial cells and in some breast cancers. Nine genes have now been identified which code for ligands. In some cases the genes are spliced into a series of proteins which differ in structure, but all retain an EGF-like element responsible for receptor recognition. The EGF receptor is expressed in normal breast and in some cancers, but is apparently reduced in expression in other cases. Cancers with EGF receptors appear to represent a greater threat to patients as in most studies they are associated with a shorter time to relapse and overall survival. The c-erbB-2 protein is overexpressed at very high levels in about one fifth of breast cancers and is indicative of poor prognosis. Other cancers may express lesser degrees of overexpression but it is not clear if this is biologically or clinically significant. The c-erbB-3 protein is expressed in normal breast epithelial cells and has been reported to be present at high levels in some cancers but at normal levels or at lower than normal levels in some others. The limited studies to date suggest that when measured on its own c-erbB-3 expression is not predictive. c-erbB-4 is also expressed in normal breast and in some cancers but no studies have yet been performed to address whether it is associated with disease behaviour. In the future it is likely that a greater understanding of the function of this complex family of interacting proteins will assist in gaining the maximum predictive power from measurement of their expression in human breast cancer.
 ...
PMID:The type 1 growth factor receptor family: new ligands and receptors and their role in breast cancer. 1006 71

Expression of the RIalpha subunit of cAMP-dependent protein kinase type I is increased in human cancers in which an autocrine pathway for epidermal growth factor-related growth factors is activated. We have investigated the effect of sequence-specific inhibition of RIalpha gene expression on ovarian cancer cell growth. We report that RIalpha antisense treatment results in a reduction in RIalpha expression and protein kinase A type I, and inhibition of cell growth. The growth inhibition was accompanied by changes in cell morphology and appearance of apoptotic nuclei. In addition, EGF receptor, c-erbB-2 and c-erbB-3 levels were reduced, and the basal and EGF-stimulated mitogen-activated protein kinase activities were reduced. Protein kinase A type I and EGF receptor levels were also reduced in cells overexpressing EGF receptor antisense cDNA. These results suggest that the antisense depletion of RIalpha leads to blockade of both the serine-threonine kinase and the tyrosine kinase signaling pathways resulting in arrest of ovarian cancer cell growth.
 ...
PMID:Protein kinase A-Ialpha subunit-directed antisense inhibition of ovarian cancer cell growth: crosstalk with tyrosine kinase signaling pathway. 1049 Aug 35

There is scant information on the cell proliferation, apoptosis, oncogenes, and tumor suppressor genes status in adenosis. Forty-eight foci of adenosis were studied with immunohistochemistry for MIB-1; c-erbB-2, c-erbB-3, bcl-2 oncogenes; and p53. To evaluate apoptosis, the TdT dUTP nick end labeling (TUNEL) method was applied. Results were compared with the same studies on benign prostatic hyperplasia (BPH) (n = 20), low-grade prostatic intraepithelial neoplasia (PIN) (n = 10); high-grade PIN (n = 20), Gleason sum 2 to 6 cancer (n = 16); and Gleason sum 7 to 10 cancer (n = 22). MIB-1 proliferation index was lowest in BPH, followed by adenosis, low-grade prostatic intraepithelial neoplasia (PIN), low-grade cancer, high-grade PIN, and high-grade cancer. The apoptotic rate was generally low in all groups, although it was higher in PIN and cancer. In BPH and adenosis, bcl-2 was absent in luminal cells. In low- and high-grade PIN, both basal and luminal cells expressed bcl-2, whereas in cancer, expression was found in only 1 case (3%). C-erbB-2 showed absent or low values for cancer and adenosis, whereas it was commonly expressed in BPH and low- and high-grade PIN. Low expression in adenosis was also found with c-erbB-3 (6%) compared with all other groups. Expression of p53 was confined to cancer. Despite a significantly higher proliferation index rate compared with BPH, adenosis showed a markedly lower proliferating index when compared with low-grade PIN, high-grade PIN, and cancer. Expression of the oncogenes c-erbB-2 and cerbB-3 was very low in adenosis, and the staining pattern for bcl-2 was similar to that of BPH. These results provide additional evidence to that of prior studies that adenosis is a histological small acinar proliferation more akin to BPH than high-grade PIN or adenocarcinoma.
 ...
PMID:Cell proliferation, apoptosis, oncogene, and tumor suppressor gene status in adenosis with comparison to benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and cancer. 1049 43

The epidermal growth factor receptor family consists of four closely related transmembrane receptors: epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3, and c-erbB-4. Overexpression of each receptor may lead to cell transformation and contributes to tumor progression in various malignancies. Although these factors have been analyzed in many cancers separately, little is known about their concomitant expression in esophageal cancer. Based on the finding that EGF-R and c-erbB-2 form highly active transmembranous heterodimers that enhance cell growth and proliferation, we used Northern blot analysis and immunohistochemistry to analyze the concomitant expression of EGF-R, c-erbB-2, and c-erbB-3 in tissue samples obtained from 39 patients undergoing esophagectomy for esophageal cancer. Northern blot analysis revealed a fourfold increase (p < 0.01) in EGF-R mRNA levels in the esophageal cancer samples in comparison with normal tissue samples. The c-erbB-2 receptor was only 1.25-fold elevated in the esophageal cancers, which failed to be statistically significant (p = 0.31). In contrast, c-erbB-3 mRNA levels were 3.5-fold lower (p < 0.01) in the esophageal cancers than in the normal tissues. Immunohistochemical analysis showed weak EGF-R, c-erbB-2, and c-erbB-3 immunostaining in the normal esophageal tissue. In esophageal cancer samples, immunoreactivity for EGF-R, c-erbB-2, and c-erbB-3 was mainly located in the cancer cells. Strong EGF-R, c-erbB-2, and c-erbB-3 immunoreactivity was present in 59%, 64%, and 64% of the esophageal cancer samples, respectively. In consecutive tissue sections, identical cancer cell clusters often exhibited these three closely related receptors simultaneously. However, correlation of the immunohistochemical findings with the clinicopathologic patient parameters revealed that the presence of EGF-R, c-erbB-2, or c-erbB-3 had no influence on patient survival (p > 0.05). In addition, the simultaneous presence of these receptors did not influence survival. Our findings indicate that in esophageal cancer the presence of EGF-R, c-erbB-2, and c-erbB-3 alone or in combination seems to have no major influence on patient prognosis and does not alter tumor growth behavior significantly.
 ...
PMID:Concomitant analysis of the epidermal growth factor receptor family in esophageal cancer: overexpression of epidermal growth factor receptor mRNA but not of c-erbB-2 and c-erbB-3. 1051 40

Members of the epidermal growth factor receptor family of tyrosine kinases, including epidermal growth factor receptor, c-erbB-2 (HER-2), c-erbB-3 (HER-3), and c-erbB-4 (HER-4), can be coexpressed at different levels in nonhematopoietic tissues. Amplification and overexpression of HER-2 is found in approximately one-third of cancers that arise in the breast and ovary. In our previous studies, heregulin (HRG) and anti-HER-2 antibodies inhibited proliferation, increased invasiveness, and enhanced tyrosine autophosphorylation of SKBr3 breast cancer cells that overexpressed HER-2. In the present report, the effects of HRG and anti-HER-2 antibody have been compared in six ovarian cancer cell lines. HRG inhibited anchorage-independent growth of SKOv3 cells that overexpressed HER-2 (10(5) receptors/cell) but stimulated the growth of OVCA420, OVCA429, OVCA432, OVCA433, and OVCAR-3 cells that expressed lower levels of the receptor (10(4) receptors/cell). Thus, cell lines with a high level of HER-2 relative to HER-3 or HER-4 were growth inhibited, whereas cell lines with lower levels of HER-2 were growth stimulated by HRG. Stimulation or inhibition of clonogenic growth did not correlate with endogenous expression of HRG or with the impact of exogenous HRG on phosphorylation of HER-2, HER-3, or HER-4. Anti-HER-2 antibodies inhibited the growth of SKOv3 cells but failed to affect the growth of the other cell lines. In OVCAR-3 cells that had been transfected with HER-2 cDNA to increase expression to 10(5) receptors/cell, HRG inhibited rather than stimulated growth. Conversely, when HER-2 expression by SKOv3 cells was downregulated by transfection of the viral E1A gene, HRG stimulated rather than inhibited growth. To evaluate the relative importance of HER-3 and HER-4, NIH 3T3 cells were cotransfected with HER-2 and HER-3 or with HER-2 and HER-4. HRG inhibited the growth of cells with a high ratio of HER-2:HER-3, whereas HRG stimulated the growth of cells with low levels of the two receptors. In cells that express only HER-2 and HER-4, HRG stimulated the growth of cells that expressed HER-4 independent of HER-2 levels. Anti-HER-2 antibodies inhibited the growth of transfectants with high levels of HER-2 expression independent of HER-3 or HER-4 expression. In ovarian cancer cells that express all three receptors, the relative levels of HER-2 and HER-3 appear to determine the response to HRG. Taken together, these studies support the concept that the level of HER-2 expression can modulate response to HRG, determining whether the response is stimulatory or inhibitory. In contrast, agonistic antibodies that bind to HER-2 alone inhibit anchorage-independent growth but fail to mimic HRG's ability to stimulate growth of cells with low HER-2: HER-3 ratios.
 ...
PMID:The outcome of heregulin-induced activation of ovarian cancer cells depends on the relative levels of HER-2 and HER-3 expression. 1058 83

Nuclear steroid/thyroid/retinoid receptors and c-erbB membrane receptor tyrosine kinases control epithelial growth and differentiation. Retinoid receptors can dimerize with the vitamin D receptor, the glucocorticoid receptor or the thyroid receptor. Furthermore, multiple c-erbB receptor dimers have been identified. It has been shown that some of these receptor pathways communicate with each other via cross-connected regulatory networks. Molecular interactions between retinoid receptors or estrogen receptors (ER) and c-erbB-2, and between ER and retinoic acid receptor(RAR)-alpha have been reported. Here, we demonstrate the effects of steroids/thyroids/retinoids and of activators of protein kinase A (forskolin, Forsk) and C (12-O-tetradecanoylphorbol-13-acetate, TPA), on growth and expression of c-erbB and RARs in MCF-7 breast cancer cells, which contain high levels of RAR-alpha and -gamma, and which express significant amounts of c-erbB-2 and -3. All trans-retinoic acid (tRA), the anti-estrogen ICI 182 780 (ICI), Forsk and TPA reduced, whereas triiodothyronine and 17beta-estradiol (E2) stimulated cell growth. Flow cytometry revealed that tRA and E2 reduced c-erbB-2 and -3, whereas tamoxifen, Forsk and TPA up-regulated c-erbB-2. c-erbB-3 was co-regulated with c-erbB-2. Northern analysis demonstrated that RAR-alpha was down-regulated by dexamethasone, ICI, and TPA, whereas vitamin D3 and E2 up-regulated RAR-alpha. RAR-gamma expression was less responsive to such treatment, being reduced only by ICI and Forsk. These data indicate that nuclear receptor and protein kinase signaling communicate with each other and control the expression of RARs and c-erbB receptors. Efficient growth control requires the coordinated interplay of both receptor systems.
 ...
PMID:Involvement of nuclear steroid/thyroid/retinoid receptors and of protein kinases in the regulation of growth and of c-erbB and retinoic acid receptor expression in MCF-7 breast cancer cells. 1067 83

The Type 1 family of growth factor receptors includes epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4. Overexpression of the first two members is associated with poorer prognosis in patients with breast carcinoma. In this study we examined the expression of c-erbB-4 protein using the monoclonal antibody HFR-1. A total of 127 consecutive cases of primary operable invasive breast carcinoma presenting between 1975 and 1977 were studied. All patients were managed by simple mastectomy or conservation surgery with radiotherapy and no adjuvant therapy given. Long-term follow-up was maintained. Routine, formalin-fixed, paraffin-embedded tumour samples were used and sections were stained immunohistochemically using the Duet StreptABC method. Immunoreactivity was classified using a simple semi-quantitative scoring method. Protein expression was generally low but definite positive cytoplasmic, membranous and nuclear reactivity was identified in 58%, 41% and 25% of cases respectively. Expression at all three sites demonstrated significant inverse associations were histological grade. In addition, membrane accentuation correlated inversely with the Nottingham Prognostic Index (NPI), while cytoplasmic reactivity showed a positive association with c-erbB-3 expression. No significant associations were found with disease-free interval or survival. The results of this study demonstrate that higher levels of c-erbB-4 protein expression are associated with a more differentiated histological phenotype in contrast to the other members of the Type 1 family. Larger series with extended follow-up will be required to ascertain definitively the prognostic value of c-erbB-4 expression in breast carcinoma.
 ...
PMID:c-erbB-4 protein expression in human breast cancer. 1073


<< Previous 1 2 3 4 5 6 Next >>