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)

Recent advances in the understanding of the molecular and genetic alterations underlying breast cancer development and progression have provided the opportunity to develop novel therapeutic strategies for this disease. None of these developments has had a greater recent impact on clinicians and pathologists than the recognition of the importance of the HER-2/neu (c-erbB-2) oncogene. Located on chromosome 17, this gene encodes a 185 kD transmembrane glycoprotein with tyrosine kinase activity that functions as a growth factor receptor. Amplification or overexpression of HER-2/neu is seen in approximately 20 to 30% of invasive breast cancers and this has been considered to be an adverse prognostic factor in many studies. However, recent interest in HER-2/neu has largely been focused on its role as a potential target for breast cancer treatment. In particular, recognition of the role of HER-2/neu in breast cancer growth led to the development of a humanized monoclonal antibody directed against the HER-2/neu protein as a therapeutic agent (Herceptin). Clinical studies have further suggested that HER-2/neu status can provide important information regarding sensitivity to certain forms of conventional systemic therapy, particularly anthracyclines. As a result of these developments, there has been increasing demand for pathologists to perform assays for HER-2/neu on current and archived breast cancer specimens. Immunohistochemistry and fluorescence in situ hybridization have emerged as the most viable assays for evaluation of HER-2/neu in routine clinical practice. However, each of these methods has its advantages and disadvantages. Determining the relative merits of these assays and developing clinically meaningful and reproducible systems to report the results are challenges pathologists must now address. The development of a therapeutic agent that directly targets a protein involved in a growth-signaling pathway represents a new paradigm in breast cancer treatment. Therapeutic strategies that target other molecules involved in breast cancer development and progression are on the horizon. It is crucial that pathologists become aware of these advances and assume a pivotal role in the development and application of assays to evaluate these new molecular targets.
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PMID:Breast cancer in the 21st century: neu opportunities and neu challenges. 1126 29

The human HER-2/neu gene encodes a 185 kDa transmembrane glycoprotein recognized by MHC class I-restricted CTLs. Here, we report that HER-2/neu peptide CTL epitopes can also be recognized by cytotoxic NK-T lymphocytes. Unfractionated peptides derived from HLA-A2(+), HER-2/neu(+) tumor cells acid cell extract (ACE), collected from patients with metastatic ovarian cancer, were used as antigen to generate in vitro cytotoxic effectors. ACE was able to elicit from cancer patients' PBMCs both alphabetaTCR(+)CD3(+)CD56(-) and alphaTCR(+)CD3(+)CD56(+) (NK-T) CTLs that lysed ACE-sensitized T2 cells in an HLA-A2-restricted manner. The same CTL lines also recognized T2 cells pulsed with HER-2/neu-derived CTL peptide epitopes, a HER-2/neu-transfected HLA-A2(+) cell line and autologous tumor cells. alphaTCR(+)CD3(+)CD56(+) CTL lines also exhibited NK-like cytotoxicity against autologous tumor cells. CTL clones were isolated from alphaTCR(+)CD3(+)CD56(+) bulk cultures displaying both MHC- and non-MHC-restricted cytotoxicity, thus confirming the dual cytolytic function of such cells. Our data demonstrate that ACE from metastatic ovarian tumors can be used as multiepitope vaccines for generating in vitro, besides classical CTLs, NK-T cells exerting efficient MHC- and non-MHC-restricted cytotoxicity against autologous tumor targets. Such NK-T cells expressing dual cytotoxic activity may prove advantageous in cancer immunotherapy.
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PMID:HER-2/neu-derived peptide epitopes are also recognized by cytotoxic CD3(+)CD56(+) (natural killer T) lymphocytes. 1194 64

The c-erbB-2 gene and its products (also designated HER-2 and c-neu) encode for a 185-kd transmembrane glycoprotein with intracellular tyrosine kinase activity. c-erbB-2 belongs to the epidermal growth factor receptor family, of which there are four known members, and has molecular homology to the epidermal growth factor receptor. It seems that this family is critical in control of growth, differentiation, and mobility of many normal and transformed epithelial cell types. We have looked for overexpression of c-erbB-2 gene product in paraffin-embedded material from 230 cases of soft tissue sarcoma, in order to establish a possible new prognostic marker and a potentially new treatment option. In all the cases, irrespective of the sarcoma histological type, the immunostaining for erbB-2 was negative. Applications of erbB-2 for prognostication as well as the option of receptor targeting by trastuzumab monoclonal antibodies were aborted.
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PMID:Lack of ErbB-2 oncogene product overexpression in soft tissue sarcomas. 1223 29

In recent years several novel prognostic determinants of breast cancer have been identified, including HER-2/neu. The oncogene called HER-2/neu or c-erbB-2 located at 17q21 encodes a 185-kD transmembrane glycoprotein, p185. The HER-2/neu gene is frequently overexpressed in human breast cancers as a result of gene amplification and/or elevated transcription. In this study we investigated the association between the presence of HER-2/neu gene ampliflcation and appearance and/or progression of breast cancer. Paraffin embedded tumour tissue was obtained from 82 women with breast cancer. Blood samples from age matched healthy women served as control (n = 50). The amplification of HER-2/neu gene was determined by PCR amplification using appropriate primers. The amplification of HER-2/neu gene was significantly higher in women with breast cancer as compared with control (P < 0.05). Additionally, there were differences in the amplification status between node-positive and node-negative breast cancer patients. The results suggest that the presence of amplification of HER-2/neu gene may be linked with the appearance and/or progression of breast cancer.
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PMID:Genetic analysis of HER-2/neu gene amplification in paraffin embedded tumour tissue in women with breast cancer. 1259 35

The HER-2/neu oncogene is located on chromosome 17q and encodes a transmembrane glycoprotein with intracellular tyrosine kinase activity. Several studies have shown an association of HER-2 gene amplification or protein overexpression with prognosis and predictor of therapeutic response. Most important, the presence of amplification or overexpression is the basis of eligibility for trastuzumab therapy. However, there are several methods of determining HER-2 status, each measuring a different aspect such as DNA content, gene copy number, protein expression, expression of RNA, and circulating HER-2 extracellular domain protein. There is no consensus with regard to the optimal test for HER-2 assessment. This review examines the various methods used in an attempt to define the most accurate and reliable test. The most widely used assays are immunohistochemical analysis and fluorescence in situ hybridization (FISH), which measure protein expression and gene amplification, respectively. Based on current data, FISH is the most accurate and reproducible test with a better correlation with prognosis and response to therapy.
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PMID:HER-2/neu evaluation in breast cancer are we there yet? 1529 49

Meningiomas account for about 15-30% of all primary intracranial tumors. According to the 2007 WHO classification, meningiomas are divided into three grades (I, II and III). Recurrence is an issue following surgical treatment of meningioma, especially in grades II and III. HER2 (also known as erbB-2) is a 185-kD transmembrane glycoprotein with tyrosine kinase activity. HER2 is expressed in some human malignancies and can be a potential target for therapeutic intervention with selective inhibitors. There are only a few studies on the relationship between meningioma and HER2 expression, and the results are different as well. The aim of this study was to determine this relationship. Seventy-two paraffin blocks of meningioma were selected randomly, and immunohistochemical staining was then performed for each specimen. Thirty-one of the 72 meningiomas were HER2-positive. HER2 expression was observed in 11 (55%) of the 20 grade II/III, and 20 (38.5%) of the 52 grade I meningiomas. Consequently, HER2 expression was detected in 43% of meningiomas. No significant difference was seen between grade I and grade II/III meningiomas, primary and recurrent tumors, and males and females from the point of view of HER2 expression.
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PMID:An immunohistochemical study of HER2 expression in meningioma and its correlation with tumor grade. 2242 Sep 24

Breast cancer is the most common cancer among women in the world. One of the approaches for diagnosis of breast cancer is detection of its tumor-associated markers. Mucin 1 (MUC1), a tumor-associated antigen, is a transmembrane glycoprotein expressed by normal epithelial cells and overexpressed by carcinomas of epithelial origin. Also, human epidermal growth factor receptor-2 (HER2/erbB-2) belongs to the one of four members of tyrosin kinase type 1 family in which overexpression of HER2 is associated with malignancy in breast cancer. This study was aimed to bioinformatics analysis and designing a recombinant chimeric protein containing MUC1 and HER2 antigens to express in prokaryotic host (Escherichia coli) as breast cancer diagnosis tools. The immunogenic sequences of MUC1 and HER2 were extracted and fused together by a linker. The chimeric construct was analyzed by bioinformatics softwares. The optimization and purification, evaluation of the expression of chimeric protein was performed using Western blotting, ELISA, and immunohistochemistry. The results showed that the chimeric construct was stable and immunogenic domains were exposed. The pET-28a vector containing chimeric gene had high level of protein expression. The recombinant chimeric protein was confirmed using Western blotting, and it was investigated using ELISA and IHC. Then, the MUC1 and HER2 combined peptides can be used as coating antigens in ELISA for detection of antibodies against MUC1 or HER2 in human serum.
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PMID:Designing a recombinant chimeric construct contain MUC1 and HER2 extracellular domain for prediagnostic breast cancer. 2512 64


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