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)

Acceleration of the polyol pathway and enhanced oxidative stress are implicated in the pathogenesis of diabetic complications. We and others recently reported that aldose reductase (AR), the rate-limiting enzyme in the polyol pathway, was upregulated by reactive oxygen and nitrogen species in vascular smooth muscle cells. To clarify the molecular mechanisms underlying these findings, we investigated the signal transduction pathways mediating AR expression using the rat vascular smooth muscle cell line A7r5. A selective epidermal growth factor (EGF) receptor kinase inhibitor, tyrphostin AG1478, significantly suppressed the hydrogen peroxide (H2O2)-induced increase in AR mRNA and enzyme activity. Activation of extracellular signal-regulated protein kinase (ERK) by H2O2 was blunted by AG1478. PD98059, a specific inhibitor of ERK kinase (MEK1), reduced H2O2-induced AR expression. EGF alone elicited activation of ERK and induction of AR expression. Increased level of AR transcript was demonstrated in cells treated with oxidized low-density lipoprotein, and this increase was also suppressed by AG1478. Inhibition of p38 MAP kinase by SB203580 also partially suppressed the H2O2-initiated AR induction. The presence of ponalrestat, an AR inhibitor, significantly accelerated H2O2-induced cell death. These results suggested that AR may act as a survival factor in these cells and that the EGF receptor-ERK pathway is the major signaling pathway involved in the upregulation of AR expression under oxidative stress.
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PMID:EGF receptor-ERK pathway is the major signaling pathway that mediates upregulation of aldose reductase expression under oxidative stress. 1144 Aug 32

The oncoprotein HER-2/neu is a prosurvival factor, and its overexpression has been correlated with poor prognosis in patients with breast cancer. We report that HER-2 is a new substrate for caspase-8 and that tumor necrosis factor alpha (TNF-alpha) stimulation leads to an early caspase-8-dependent HER-2 cleavage in MCF7 A/Z breast adenocarcinoma cells defective for nuclear factor kappaB (NFkappaB) activation. We show that the antiapoptotic transcription factor NFkappaB counteracts this cleavage through induction of the caspase-8 inhibitor c-FLIP. Our results also demonstrate that this HER-2 cleavage contributes to the TNF-alpha-induced apoptosis pathway because ectopic expression of an uncleavable HER-2 protects NFkappaB-defective cells against TNF-alpha-mediated cell death. Therefore, we propose an original model in which NFkappaB exerts a new antiapoptotic function by counteracting TNF-alpha-triggered cleavage of the HER-2 survival factor.
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PMID:Caspase-8-dependent HER-2 cleavage in response to tumor necrosis factor alpha stimulation is counteracted by nuclear factor kappaB through c-FLIP-L expression. 1508 80

VEGF is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathological conditions. Nevertheless, VEGF tissue evaluation in cancer patients as a prognostic factor compared to the conventional histological and biological parameters is still controversial. In this case-control study, tissue VEGF was retrospectively determined by immunohistochemistry and related to T, N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 in 129 breast cancer patients. Seventy-four of these patients had developed distant metastases postoperatively. The remaining 55 patients had remained disease-free >10 years after surgery. In 17 (13%) of the 129 patients (six with distant metastases and eleven disease-free) tissue and plasma VEGF were concomitantly evaluated. In univariate analysis no significant differences in VEGF and tumor size were found between metastatic and disease-free patients, whereas there were significant differences in N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 (p ranging from 0.001 to 0.0001). In multivariate analysis VEGF showed less significance than N, ER, c-erbB-2, MIB-1 and cyclin D1 (p = 0.012, p = 0.007, p = 0.005, p = 0.005, p = 0.002 and p = 0.001, respectively). VEGF was a significant unfavorable prognostic indicator only in the N+ subset (p = 0.015), while ER (p = 0.05 and p = 0.021) and MIB-1 (p = 0.031 and p = 0.022) were significant in both the N+ and N- subgroups. In multivariate analysis in the 74 metastatic cases VEGF did not show any significance in relation to disease-free interval and overall survival from the time of mastectomy and from the time of relapse, whereas N and PgR did (p ranging from 0.018 to 0.001). In conclusion, tissue VEGF does not seem a suitable candidate to replace conventional histological and other common biological prognostic factors in breast cancer.
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PMID:Vascular endothelial growth factor (VEGF) and other common tissue prognostic indicators in breast cancer: a case-control study. 1564 33