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 etiology of cancer is a complex interplay of various factors, including genetic alterations. Multiple studies have been carried out to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, amplification of proto-oncogenes (c-myc, c-erbB-2/neu) and chromosome 11q13, mutation of p53 and loss of heterozygosity (chromosomes 1, 3p, 6q, 7q, 11p, 13q, 16q, 17, 18q and 22q) represent the major types of genetic abnormalities that have been frequently observed in tumor DNAs. The genetic deletions and mutations could inactivate tumor-suppressor genes. In some studies, specific alterations have been associated with some clinical parameters. Recently, linkage analyses, on large families with a predisposition to breast cancer, have been performed to map putative breast cancer susceptibility genes. The survey of high risk patients should be organised to make an earlier diagnosis.
 ...
PMID:[Molecular analysis of breast cancers: recent developments]. 130 32

The expression of the protooncogene encoded proteins (c-erbB1, c-erb B2, c-myc, c-fos) and the suppressor gene product p53 was analyzed in 81 human squamous cell carcinomas of the lung and correlated with clinical parameters of the patients (patient survival, presence of metastases and tumor stage) and with biological characteristics of the tumors (tumor growth in nude mice, DNA-ploidy, proliferative activity, drug-resistance and P-glycoprotein or gluathione S-transferase expression). By means of immunohistochemistry, expression of c-erbB1 oncoprotein (EGF-receptor) was detected in 79% of the tumors, c-erbB2 (c-neu) proteins in 35%, c-myc proteins in 48%, c-fos proteins in 41%, and p53 in 43% of the tumors. Patients with c-erbB1 positive tumors had a poor prognosis (p = 0.021). In addition, these tumors were more frequently drug resistant (p = 0.0067). A significant correlation between the growth of the squamous lung carcinomas in nude mice and c-fos oncoprotein expression was demonstrated (p = 0.017). Therefore, EGF-receptor and c-fos products may serve as prognostic factors for the aggressiveness of squamous cell carcinomas of the lung and for the response of these tumors to chemotherapy. No significant correlation was found between the expression of the c-erbB1 or c-fos gene products and stage, metastasis and DNA-ploidy. In contrast to these results, no relationship was found between c-neu or c-myc gene products expression and any of the clinical or biological parameters examined. Aneuploid squamous cell carcinomas of the lung expressed p53 more frequently than diploid tumors (p = 0.027). However, there was no significant difference between p53 expression and stage, survival of patients, metastasis, growth of the tumors in nude mice, proliferative activity and drug-resistance of the tumors.
 ...
PMID:Oncoprotein (c-myc, c-erbB1, c-erbB2, c-fos) and suppressor gene product (p53) expression in squamous cell carcinomas of the lung. Clinical and biological correlations. 134 20

c-myc, c-erbB-2, and Ki-67 expression was examined by immunohistochemistry in 11 normal breast tissues and 42 invasive and 14 noninvasive breast carcinomas. The c-myc product was detected in all breast carcinoma specimens and in 7 of 11 normal breast tissues. Invasive tumors stained more frequently with the anti-myc monoclonal antibody than did noninvasive tumors, while the level of expression in normal breast tissue was much less than that in breast cancer. Membrane staining of the c-erbB-2 protein was demonstrated in 29% (4 of 14) of noninvasive ductal carcinomas and in 45% (19 of 42) of invasive breast carcinomas. None of the 11 normal breast tissue samples was positive. The mean value of Ki-67-positive cells was 0.91 +/- 0.31% for normal breast tissue, 4.57 +/- 1.36% for noninvasive ductal carcinoma, and 12.76 +/- 2.18% for invasive breast cancer. In 42 invasive breast carcinomas, the expression of c-myc, c-erbB-2, and Ki-67 proliferation marker were compared with lymph node status, estrogen receptor status, progesterone receptor status, and age of patients at diagnosis. c-erbB-2 overexpression and Ki-67 overexpression were identified as the only factors associated with lymph node status. We concluded that they might be additional prognostic factors for breast carcinoma.
 ...
PMID:c-myc, c-erbB-2, and Ki-67 expression in normal breast tissue and in invasive and noninvasive breast carcinoma. 134 67

The expression of oncogene products related to cell growth (c-erbB-2, c-myc, ras p21, EGFR) was investigated in benign (15 cases) and malignant breast lesions (20 cases) by means of immunohistochemistry using the avidin-biotin-peroxidase technique with polyclonal and monoclonal antibodies. The aim of this study was to evaluate the relationship between the staining positivity and various morphological and biological features, such as tumour type, grading, hormone receptor status and cell kinetic parameters. In benign breast lesions, as expected, the kinetic parameters were low, both for Ki-67 and LI. All the specimens showed a diploid condition (the DI being equal to 1) and we found a limited degree of immunoreactivity for all the growth factors and oncogene products. In breast cancer we studied the distribution of immunohistochemical positivity for EGFR, c-erbB-2, c-myc, ras p21 and Ki-67, which was related to age, nodal status, ER and PgR receptor status, LI, DI and histopathological grading. A significant positive correlation was found both between ras p21 expression and nodal status and ER-ICA positivity. We observed a strong correlation between LI and Ki-67 and an inverse relation between Ki-67 and ER expression. These findings suggest the importance of studying the relationship between prognostic factors which may provide preoperative prediction in the biological behaviour of breast cancer, not only on biopsy specimens, but also on fine needle aspirates.
 ...
PMID:Preliminary study on oncogene product immunohistochemistry (c-erbB-2, c-myc, ras p21, EGFR) in breast pathology. 134 7

In order to identify potential markers of malignancy in diagnostic respiratory cytopathology, c-myc and c-erbB-2 proto-oncogene expression was studied in fine needle aspirates from 14 consecutive fresh operation tissue samples (after surgical removal) representing lung tumors and a variety of other cell samples by in situ hybridization of 35S-labeled antisense and sense RNA c-myc and c-erbB-2 specific proto-oncogene probes. All 14 lung tumors showed c-myc expression and eight also showed c-erbB-2 expression. On average, the c-myc expression was about 4 times higher than that of c-erbB-2 (P less than 0.001). c-erbB-2 expression, confirmed also as a cytoplasmic membrane-bound reactivity by immunohistochemical stainings for c-erbB-2 oncoprotein, was significantly related to adenocarcinoma (P less than 0.025), whereas increasing tumor size correlated significantly with increasing c-myc expression (P less than 0.05). On average, all the tumor cell lines showed 2-fold expression of c-myc compared with the lung tumors (P less than 0.025). c-erbB-2 expression was found in six of 11 cell lines. High c-myc proto-oncogene expression was also found in broncho-epithelial cells and alveolar macrophages, and a low expression was found in lymphocytes but not in neutrophils, while none of these cells showed c-erbB-2 proto-oncogene expression. Our results demonstrate extensive c-myc proto-oncogene expression in both malignant and non-neoplastic proliferating cells, but not in terminally differentiated cells such as neutrophils. Therefore c-myc expression must also be related to general cell proliferation and not only malignancy per se. In marked contrast, c-erbB-2 proto-oncogene expression was found only in adenocarcinoma cells, and thus can be used as a marker for malignancy in diagnostic respiratory cytopathology.
 ...
PMID:Evidence by in situ hybridization that c-erbB-2 proto-oncogene expression is a marker of malignancy and is expressed in lung adenocarcinomas. 135 55

In breast cancers with histologically negative axillary nodes selected for high frequency of recurrence, the amplification of c-myc, erbB-2 and int-2 genes was found to concern, respectively 25% (16/65), 31% (25/81) and 14% (10/70) of tumours. Their relation with tumour progression expressed by relapse-free survival is reported. Using univariate analyses, c-myc amplified tumours showed significant association with early (30-month period after diagnosis) (P = 0.0013) and intermediate (50-month period after diagnosis) (P = 0.0398) risks of recurrence. In contrast, only a trend towards higher relapse was observed in erbB-2 amplified breast cancers with respect to later events (occurring over the first 30-month period). Multivariate analyses indicated that c-myc amplification is an independent prognostic factor stronger than oestrogen receptor status and tumour size to define a high risk subset in node-negative patients selected for high frequency of recurrence.
 ...
PMID:c-myc gene amplification in selected node-negative breast cancer patients correlates with high rate of early relapse. 135 87

A new cell line, designated BSMZ, was established from a malignant pleural effusion from a woman with breast cancer. This line has a doubling time of 27 h and has now been cultured for over 120 passages. The large, rounded BSMZ cells grow as both a monolayer and as aggregations in suspension. Intracytoplasmic lumen, a finding consistent with results from cells derived from mammary tissue, was detected on ultrastructural analysis. Injection of BSMZ cells into nude mice resulted in the growth of solid tumors 4 weeks after inoculation. The solid tumor was identical to the original BSMZ cells in microscopic and electron microscopic studies. These cells possess an average of 80 chromosomes. Expression of erbB-2 and c-myc genes was increased by 10-fold, while there was no detectable overexpression of the N-ras and c-myb genes. Southern analysis has revealed amplification of the erbB-2 and c-myc loci. The BSMZ cell line may therefore provide a useful model for the study of human breast cancer and overexpression of the erbB-2 gene.
 ...
PMID:Establishment of the human BSMZ breast cancer cell line, which overexpresses the erbB-2 and c-myc genes. 135 15

Genetic alterations of various cancers have been clarified by recent development of molecular biology. Multiple genetic alterations occur through the development of cancer. Both activation of proto-oncogenes and inactivation of tumor suppressor genes are important for the development of cancer. Alterations of oncogenes such as K-ras, c-erbB-2/HER-2/neu and c-myc, and those of tumor suppressor genes such as p53, RB and DCC have been reported in ovarian cancer. Allelic losses of the specific chromosomes, which suggest the existence of tumor suppressor genes on those chromosomes, also have been reported in ovarian cancer. Further studies on genetic alterations of ovarian cancer will clarify the mechanisms for the development of ovarian cancer and also will develop new methods for prevention, diagnosis and treatment in clinical.
 ...
PMID:[Genetic alterations in the genesis and development of ovarian cancer]. 135 31

In summary, evidence is beginning to accumulate in support of a major role for tyrosine kinase receptors (and their activating growth factors) and steroid hormones and their receptors in normal development and differentiation of the mammary gland. A point of intersection of their mechanisms of action in growth control appears to be the induction of nuclear protooncogenes such as c-myc. When c-myc is amplified, as it is in many breast cancers, EGF and FGF receptor tyrosine kinase action becomes transforming, not simply mitogenic. A source of the transforming factors could be either stromal or epithelial. This mechanism could function early in the progression of breast cancer. c-erbB-2 and EGF receptor overexpression and amplification, when they occur, appear to render tumors even more malignant and of especially poor prognosis. These mechanisms could function late in the progression of breast cancer. Transgenic mouse studies have begun to echo these themes. They have established that a growth factor (TGF-alpha) and its receptor (EGF receptor), which appear to be important in normal mouse and human proliferation and gland development, and a protooncogene (c-myc), commonly amplified and overexpressed in human and mouse breast cancer, can each contribute to mammary carcinogenesis. The mechanisms of the two are likely to be distinct. myc is likely to be acting as a tumor initiator in combination with normal proliferative factors, whereas TGF-alpha is likely to be acting as a hyperproliferative (promotional) factor in combination with a normal background of mutational events. The role of unmutated but amplified erbB-2 in the transgenic mouse is not yet known.
 ...
PMID:Tyrosine kinase receptor--nuclear protooncogene interactions in breast cancer. 136 Feb 36

Oncogene expression has been found to be a potential marker for aggressive biologic behavior in certain tumors. We studied 21 follicular adenomas and 20 follicular carcinomas by immunocytochemistry utilizing specific monoclonal antibodies against HER-2/neu and c-myc oncogenes. Survival data were obtained from our institution's tumor registry. No expression of the HER-2/neu oncogene was found in the specimens studied. Cytoplasmic staining for c-myc was observed in 3 of 21 adenomas (14%) and 9 of 20 (45%) carcinomas (p < 0.05). The incidence of local, regional, and distant metastases was not significantly different in c-myc (+) and c-myc (-) patients. The c-myc oncogene is expressed more often in malignant than in benign follicular neoplasms of the thyroid, but its expression does not appear to be a good prognostic indicator.
 ...
PMID:Oncogene expression in follicular neoplasms of the thyroid. 136 Nov 6


1 2 3 4 5 6 7 8 9 10 Next >>