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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patient group with breast carcinoma with one to three axillary lymph-node metastases (n1-3) shows a poorer prognosis than the node-negative one but a better prognosis than the group with 4 or more lymph node metastases. Univariate analysis shows that loss of bc1-2 expression, nuclear accumulation of p53, overexpression of c-erbB-2, age at diagnosis, menstrual status, tumor size, histologic grade, number of lymph nodes involved, and estrogen receptor were all significantly associated with the survival rates. Multivariate analysis demonstrated that menstrual status, number of involved lymph nodes, bc1-2, and p53 were significant predictors for overall survival, and that histological grade and number of nodes involved were significant predictors for disease-free survival. Combination of those factors would be useful to select highly aggressive n1-3 breast cancer group.
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PMID:[Value of cancer-related oncoprotein expression as prognostic factors in breast-cancer with one to three axillary lymph nodes positive]. 870 14

We have studied by immunohistochemistry the nuclear expression of p53 and the finding of oncoprotein c-erbB-2 in a series of 85 breast carcinomas. The tissue was fixed in buffered formalin and embedded in paraffin. The primary antisera were obtained from Biogenex (USA), Bp53-12, monoclonal, used in a dilution of 1:100 for p53 and from Triton Diagnostics (USA), pAB-1, polyclonal, used in a dilution of 1:200 for c-erbB2. The detection system was the Vectastain Elite kit obtained from Vector Laboratories (USA). The results were compared with several morphological features of the tumors such as size and type of the tumor, extension of the intraductal component, nuclear grade, axillary lymph node metastasis and estrogen receptor data as well as with total and disease free survival. The oncoprotein p53 was detected in the nuclei in 25 (29.4%) of our cases (Fig 1). Its presence was correlated with tumor size (p < 0.01), high nuclear grade (p < 0.0001) and estrogen receptor negative tumors (p < 0.0001). There was an inverse relationship between p53 expression and 5 year disease free survival (p < 0.005). In 21 (24.7%) of the cases we found amplification of c-erbB-2. The staining pattern was membranous (Fig. 2). It was correlated significantly with the ductal type of invasive carcinoma (p < 0.05), an associated extensive intraductal component (p < 0.001), estrogen receptor negative tumors (p < 0.0001) and shortening of disease free survival in the patients with positive axillary lymph nodes (p < 0.005). In 9 cases we found staining for both markers without statistically significant relationship with the other features studied. We conclude that the presence of these genetic alterations demonstrated by immunohistochemistry were, in our series, unfavourable prognostic factors in invasive breast cancer.
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PMID:[Immunohistochemical analysis of p53 and c-erbB-2 in breast cancer]. 872 71

The expression of c-erbB-2 oncoprotein, epidermal growth factor receptor (EGFR) and estrogen receptor (ER) was evaluated by the immunoperoxidase technique (PAP) in ductal breast carcinomas. The relationship between these cell growth regulatory factors was considered and compared with tumor grading, tumor size, lymph node involvement and age of patients. Stratifying of patients on the basis of c-erbB-2, EGFR and ER status indicated that the combination of c-erbB-2 overexpression accompanied by high EGFR value and undetectable ER, identified poorly differentiated tumors and patients with high incidence of axillary lymph node metastases, while high EGFR expression and negative c-erbB-2 staining was connected only with poor tumor grade. The undetectability of molecular markers was associated with higher histological grade and lack of lymph node involvement. Our results indicate that the comparison of c-erbB-2, EGFR and ER status seems to be a powerful tool in discriminating breast carcinomas with different biological phenotypes.
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PMID:Relationship between c-erbB-2 oncoprotein, epidermal growth factor receptor, and estrogen receptor expression in patients with ductal breast carcinoma. Association with tumor phenotypes. 874 3

The erbB-2 receptor plays an important role in the prognosis of breast cancer. Amplification or overexpression of the erbB-2 proto-oncogene has been detected in 30% of breast cancers and is associated with poor patient prognosis. The significance of erbB-3 and erbB-4 in breast cancer is not yet known. The discovery of the growth factor heregulin (HRG) has allowed us to investigate a number of biological events that are regulated by erbB-2, -3, and -4 signal transduction. To determine the role of HRG in breast cancer tumor progression, we have developed an in vitro/in vivo model. We transfected HRG cDNA into the estrogen receptor (ER)-positive breast cancer cell line, MCF-7, and studied these cells as they progressed from a hormone-dependent to -independent phenotype. The biochemical and biological characteristics presented here demonstrate that overexpression of HRG induces morphological changes in MCF-7 cells as well as erbB-2, erbB-3, and erbB-4 autophosphorylation. MCF-7/ heregulin-transfected cells, which express relatively high levels of HRG, developed estrogen independence and resistance to antiestrogens in vitro and in vivo. This is consistent with a more aggressive hormone-independent phenotype. In contrast with control parental/wild-type cells, estradiol-mediated down-regulation of erbB-2 expression is blocked completely in this particular model system. These results indicate that HRG plays a role in the disruption of ER function. When a transient transfection with an ERE-CAT construct was introduced into these HRG-transfected MCF-7 cells, we observed that the ER was transcriptionally inactive. This suggests that ER signaling is altered in HRG-transfected cells. We observed that overexpression of HRG induces a more aggressive, hormone-independent phenotype that is most likely directly related to the constitutive activation of the erbB-2, erbB-3, and erbB-4 receptor signaling cascade. The data presented here suggest a close cross-regulation between the erbB-2/4 receptors and ER and provide new insights into the mechanism by which breast cancer cells acquire a hormone-independent phenotype.
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PMID:Involvement of heregulin-beta2 in the acquisition of the hormone-independent phenotype of breast cancer cells. 876 33

In breast cancer, epidermal growth factor (EGF) receptor (EGFR) expression is inversely correlated with expression of estrogen receptor (ER) and predicts the prognosis and failure of endocrine therapy. We report here, for the first time, that in ER-positive breast cancer cell lines, MCF-7, T47D, and BT474, 17 beta-estradiol (E2) transiently induced EGFR messenger RNA (mRNA) levels 2- to 3-fold; this induction was prevented by the presence of the antiestrogen ICI 164,384 and was also reflected in the level of EGFR protein. Up-regulation of EGFR mRNA is most likely due to a direct effect of ER on the EGFR gene, with no involvement of protein synthesis, as it was not inhibited in the presence of cycloheximide; however, the subsequent down-regulation of EGFR required de novo protein synthesis. E2 had no effect on EGFR mRNA stability, and EGFR transcript levels were found to parallel EGFR mRNA levels, further supporting a direct transcriptional mechanism in the regulation of EGFR expression by estrogens. Additionally, sequencing of the EGFR promoter revealed putative imperfect estrogen-responsive elements that were capable of binding human ER. The transient nature of EGFR induction by E2, with a rapid return to a basal level that is dependent on protein synthesis, suggests that breast cancer cells possess active mechanisms to maintain low levels of EGFR expression in the presence of estrogen and a functional ER.
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PMID:Bimodal regulation of epidermal growth factor receptor by estrogen in breast cancer cells. 877 Aug 93

The proliferative activity in 35 cases of breast carcinoma was evaluated by bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) and was compared with benign breast lesion. Overexpression of p53 and c-erbB-2 oncoprotein, presence of estrogen receptor (ER) and cellular localization of multidrug resistance gene product P-glycoprotein (P-gp) were immunohistochemically examined to investigate the relation with the proliferative activity and clinicopathologic characteristics. The mean BrdU labeling index (LI) was 12.6% and PCNA labeling rate (LR) was 33.5% in breast carcinomas, and good correlation was found between them. The proliferative activity of breast carcinomas was significantly higher than that of benign lesions. The BrdU LI correlated positively with tumor size, histologic grade, TNM stage and p53 immunoreactivity, and negatively with the presence of ER. PCNA LR correlated with histologic grade and expression of p53. p53 protein was demonstrated in 43% of the breast carcinomas and correlated with proliferative activity. The extent of p53 immunoreactivity on carcinoma cells was also related to BrdU LI. c-erbB-2 oncoprotein was demonstrated in 51% of the breast carcinomas and correlated with histologic grade. ER was found in 34% of the breast carcinomas and correlated negatively with histologic grade, lymph node metastasis and TNM stage. P-gp was observed in 49% of the breast carcinomas and no correlation was found with clinicopathologic characteristics. None of the benign lesions expressed p53 protein, c-erbB-2 oncoprotein and P-gp. BrdU is a reliable standard and a more useful tool for the evaluation of proliferative activity of breast tumors. High proliferative activity, overexpression of p53 protein and the absence of ER are considered as a high grade malignancy of breast carcinoma. Expression of c-erbB-2 oncoprotein and P-gp may be related to malignant transformation of breast tumors.
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PMID:Proliferative activity in breast carcinoma evaluated by BrdU and PCNA. Correlation with expression of p53, c-erbB-2, estrogen receptor and P-glycoprotein. 882 14

Expression of the erbB-2 oncogene in breast cancer patients correlates with poor prognosis and failure of hormonal therapy. In this study, the effects of a putative erbB/HER ligand, gp30, on estrogen receptor (ER) concentration and activity was investigated in the estrogen receptor positive human breast cancer cells, BT474 and MCF-7, which express either high or low levels of erbB-2 and erbB-4, respectively. Treatment of cells with gp30 resulted in a decrease in the steady-state level of estrogen receptor protein by approximately 70-80%. The effect of gp30 on the concentration of ER was independent of serum in the media and was not inhibited by an epidermal growth factor receptor blocking antibody. In addition to the effect on ER protein, gp30 decreased the steady-state level of ER messenger RNA. Transcription run on experiments demonstrated that the decrease in ER expression was mediated by a decrease in ER gene transcription. The effect of gp30 on estrogen receptor activity was also investigated in this study. Treatment of cells with gp30 blocked estradiol induction of progesterone receptor. Inhibition was observed at the level of progesterone receptor protein, messenger RNA, and gene transcription. gp30 also blocked estradiol induction of pS2 gene transcription. In addition to its effects on progesterone receptor and pS2, gp30 blocked activation of an estrogen response element in a transient transfection assay and inhibited ER binding to its response element in a DNA mobility shift assay, suggesting a direct effect on the estrogen receptor. The effects of gp30 on estrogen receptor concentration and activity were independent of the level of erbB-2 and erbB-4 in the cell. These data show that gp30 regulates the concentration of ER and modulates ER activity.
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PMID:Regulation of estrogen receptor concentration and activity by an erbB/HER ligand in breast carcinoma cell lines. 882 92

Thirty cases of invasive ductal carcinoma of the breast were classified to histological subtype according to the General Rules for Clinical and Pathological Recording of Breast Cancer of the Japanese Breast Cancer Society and histologically graded using the Nottingham method and the correlation of histology with proliferative activity was investigated using bromodeoxyuridine (BrdU). In addition, the overexpression of p53 protein, c-erbB-2 oncoprotein and estrogen receptor (ER) were immunohistochemically examined in order to discuss the relationship with histological subtype and histological grade. Histological grade correlated positively to the BrdU labeling index (LI) and overexpression of p53. High grade carcinoma demonstrated c-erbB-2 more frequently and exhibited a low incidence of ER. However, no significant relationship was found between BrdU LI, overexpression of p53 and c-erbB-2 and histological subtype. These results suggest that the histological grade does represent the proliferative activity of tumor cells and that adding the histological grade to the pathological diagnosis in invasive ductal breast carcinoma may be useful from the clinicopathological aspect concerning tumor behavior.
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PMID:Histological grade in invasive ductal carcinoma of breast correlates with the proliferative activity evaluated by BrdU: an immunohistochemical study including correlations with p53, c-erbB-2 and estrogen receptor status. 886 93

Two new immunoenzymatic assays for c-erbB-2 oncoprotein and epidermal growth factor receptor (EGF-R) (Oncogene Science) in human breast cancer were validated. Correlations between these assays and some clinical and biological parameters were also studied. The repeatability and reproducibility of standard curves for the two methods gave a coefficient of variation (CV) of less than 4% and about 10% respectively. The accuracy of c-erbB-2 oncoprotein and EGF-R assays was examined by using dilution and recovery tests throughout the standard curves. The linear relations between theoretical and measured values, for these tests, had slopes close to 1 and an intercept near 0. The median value for EGF-R, measured on solubilized membranes of 290 primary tumors, was 0.12 fmol/micrograms protein, the mean value was 0.37 (range 0 to 35.7). For c-erbB-2 oncoprotein, the median value, measured using the same population, was 2.75 human neu unit/micrograms protein, the mean value was 7.85 (range 1 to 125). There was an inverse relationship between EGF-R values and those for the estrogen receptor (ER), progesterone receptor and pS2 protein as well as menopausal status. C-erbB-2 oncoprotein concentrations were positively correlated with ER, pS2 protein and cathepsin D. Furthermore, a significant positive correlation was observed between EGF-R levels and c-erbB-2 oncoprotein levels. In conclusion, immunoenzymatic assays of EGF-R and c-erbB-2 oncoprotein are easy to use, sensitive and reliable. The accurate standardisation of immunoenzymatic assays could contribute to the clinical use of EGF-R and c-erbB-2 oncoprotein as prognostic factors in breast cancer.
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PMID:[Immunoenzymatic assays of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer: correlation with clinical and biological parameters]. 888 58

This review of published data on the epidemiology, pathology, and molecular biology of breast cancer in African American women seeks to identify how the etiology and presentation of the disease differ from those in white women. The crossover from higher to lower age-specific incidence rates in African American women at age 45 cannot be explained by current data on the distribution of risk factors. Data from six case-control studies suggest that the relative risks associated with both established and probable breast cancer risk factors are similar in African American and white women. Lower survival in African American compared to white women is primarily attributable to diagnosis at a later stage. However, evidence from a number of studies suggests that tumors in African American women may exhibit a more aggressive phenotype, which could also contribute to the survival disparity. Tumors in African American women are more likely to occur at a younger age, to be poorly differentiated and estrogen receptor negative, and to exhibit high grade nuclear atypia, more aggressive histology (more medullary and less lobular), and higher S-phase. Overexpression of p53 and erbB-2 occurs with similar frequency in African American and white women, although limited data suggest the former may exhibit different p53 mutation spectra. One study found high risk associated with a specific CYP1A1 polymorphism in African American but not white women. Additional studies of molecular differences in African American and white women are needed, with multifactorial assessment of the independent effects of molecular and conventional risk attributes.
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PMID:Breast cancer in African American women: epidemiology and tumor biology. 888 49


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