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)

Expression of cyclooxygenase-2 (COX-2) has been linked to many cancers and may contribute to malignant phenotypes, including enhanced proliferation, angiogenesis, and resistance to cytotoxic therapies. Malignant gliomas are highly aggressive brain tumors that display many of these characteristics. One prominent molecular abnormality discovered in these astrocytic brain tumors is alteration of epidermal growth factor (EGF) receptor (EGFR) through gene amplification and/or mutation resulting in excessive signaling from this receptor. We found that EGF-mediated stimulation of EGFR tyrosine kinase in human glioma cell lines induces expression of both COX-2 mRNA and protein. The p38 mitogen-activated protein kinase (p38-MAPK) pathway was a strong downstream factor in this activation with inhibition of this pathway leading to strong suppression of COX-2 induction. The p38-MAPK pathway can activate the Sp1/Sp3 transcription factors and this seems necessary for EGFR-dependent transactivation of the COX-2 promoter. Analysis of COX-2 promoter/luciferase constructs revealed that transcriptional activation of the COX-2 promoter by EGFR requires the Sp1 binding site located at -245/-240. Furthermore, Sp1/Sp3 binding to this site in the promoter is enhanced by EGFR activation both in vitro and in vivo. Enhanced DNA binding by Sp1/Sp3 requires p38-MAPK activity and correlates with increased phosphorylation of the Sp1 transcription factor. Thus, EGFR activation in malignant gliomas can transcriptionally activate COX-2 expression in a process that requires p38-MAPK and Sp1/Sp3. Finally, treatment of glioma cell lines with prostaglandin E2, the predominant product of COX-2 activity, results in increased vascular endothelial growth factor expression, thus potentially linking elevations in COX-2 expression with tumor angiogenesis in malignant gliomas.
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PMID:EGFR activation results in enhanced cyclooxygenase-2 expression through p38 mitogen-activated protein kinase-dependent activation of the Sp1/Sp3 transcription factors in human gliomas. 1761 68

Angiogenesis, formation of new blood vessels from a preexisting vascular bed is a complex multistep process, which may also permit metastasis. The subset of patients with breast cancer demonstrating a c-erbB-2 (HER2/neu)-positive status has aggressive tumors and a poor prognosis. To investigate how tumor angiogenesis correlates with c-erbB-2 (HER2/neu) overexpression in breast carcinoma diagnosed on core biopsy, microvessels were counted (and graded the density of microvessels) within the initial invasive carcinomas of 158 patients. Using light microscopy, the number of microvessels was counted manually in a subjectively selected hot spot (in the most active areas of neovascularization per 400x field), and their values were separated as above or below median (low and high), without knowledge of the outcome in the patient or any other pertinent variable. When the mean values of MVD of the various groups defined by c-erbB-2 (HER2/neu) overexpression were compared, significant difference was noted (P = 0.014818). When tumors were classified as high or low MVD, based on a cut-off value (30.70175 microvessels/mm(2)), cases with high MVD were significantly more numerous. MVD did show a relationship with groups defined by c-erbB-2 (HER2/neu) status (P = 0.002699) or c-erbB-2 (HER2/neu) score (P = 0.027589). The correlation of angiogenesis with c-erbB-2 (HER2/neu) overexpression may be a potential therapeutic target for the treatment and prevention of breast cancer, using antiangiogenic molecules.
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PMID:Angiogenesis and c-erbB-2 (HER2/neu) overexpression status in primary breast cancer patients: an analysis of 158 needle core biopsies. 1764 98

Formation of new blood vessels from a preexisting vascular bed (angiogenesis) is a complex multistep process, which may also permit metastasis. High c-erbB-2 (HER2/neu) expression has also been shown to correlate with tamoxifen resistance in patients in some studies. To investigate how tumor angiogenesis correlates with co-expression ER/c-erbB-2 (HER2/neu) in breast carcinoma diagnosed on core biopsy, microvessels were counted (and graded the density of microvessels) within the initial invasive carcinomas of 158 patients. Using light microscopy, the number of microvessels was counted manually in a subjectively selected hot spot (in the most active areas of neovascularization per 400x field), and their values were separated as above or below median (low and high), without knowledge of the outcome in the patient or any other pertinent variable. When tumors were classified as high or low MVD, based on a cut-off value (30.70175 microvessels/mm(2)), cases with high MVD were significantly more numerous. When the mean values of MVD of the various groups defined by co-expression ER/c-erbB-2 (HER2/neu) were compared, significant difference was noted (P = 1.82E-05). MVD did show a relationship with groups defined by co-expression ER/c-erbB-2 (HER2/neu) (P = 0.000422). Combining endocrine treatment with these new-targeted therapies (using antiangiogenic molecules) is a promising approach to improve present treatment strategies and overcome endocrine resistance and should be investigated in future preclinical and clinical studies.
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PMID:Angiogenesis and co-expressed of ER and c-erbB-2 (HER2/neu) protein in primary breast cancer patients: an analysis of 158 needle core biopsies. 1905 Jul 94

Several data support a central role for angiogenesis in breast cancer growth and metastasis. Observational studies have demonstrated that microvascular density (MVD) is a prognostic factor in invasive breast cancer, whereas others reached the opposite conclusion. Vascular endothelial growth factor is the most important angiogenic factor with proven significance in breast cancer, as it has been assessed in both experimental and clinical studies. Triple-negative breast cancer (TNBC) is a type of breast cancer which lacks estrogen, progesterone, and HER-2/neu receptors. MVD in both basal-like and TNBC is significantly higher than in non-basal-like and non-TNBC. In breast cancer and other malignancies, the development of agents that inhibit tumor angiogenesis has been an active area of investigation. In TNBC, clinical trials combining targeted agents and chemotherapy have failed to show substantial survival improvement. There is evidence that patients with TNBC may have a greater probability of obtaining some kind of clinical efficacy benefit from bevacizumab-based therapy.
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PMID:Angiogenesis and Antiangiogenesis in Triple-Negative Breast cancer. 2775 50


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