Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of HER2/neu-overexpressing target cells with interferon gamma (IFN gamma) (200-2000 U/ml for 3 days) markedly enhances their sensitivity to lymphokine-activated killer (LAK) cell lysis. Increased sensitivity is associated with an up-regulation of intercellular adhesion molecule ICAM-1 determinants and a down-regulation of HER2/neu expression. In the present study, we show that exposure to another cytokine, tumor necrosis factor alpha (200 U/ml for 3 days), also decreased HER2/neu expression but had no effect on LAK cell lysis and ICAM-1 expression. This suggests that down-regulation of oncogene expression is not sufficient by itself to induce an enhanced sensitivity to LAK cell lysis. IFN-induced enhanced lysis was associated with an increased binding between effectors and targets, and antibodies to ICAM-1 as well as its counter-receptor LFA-1, blocked the increased binding and lysis. Treatment with IFN gamma still significantly enhanced lysis even when concanavalin A was added to the assay to induce maximal binding, indicating that a post-binding effect also participated in enhanced cytotoxicity. These post-binding alterations, were also sensitive to blocking with anti-ICAM-1 and anti-LFA-1 antibodies. Treatment with IFN also sensitized targets to lysis by T cells in the presence of lectin but had no effect on the relative resistance of HER2+ cells to lysis mediated by perforin or TNF. Together these data demonstrate the importance of ICAM-1 determinants in binding and post-binding events in the IFN-induced increased lysis of HER2/neu+ targets.
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PMID:Interferon-gamma-induced increased sensitivity of HER2/neu-overexpressing tumor cells to lymphokine-activated killer cell lysis: importance of ICAM-1 in binding and post-binding events. 810 95

The molecular changes associated with the transition of melanoma cells from radial growth phase (RGP) to vertical growth phase [(VGP), metastatic phenotype] are not very well defined. We previously demonstrated that expression of the cell-surface adhesion molecule MCAM/MUC18 correlates directly with the metastatic potential of human melanoma cells. In addition, the progression of human melanoma towards the metastatic phenotype is associated with loss of expression of the tyrosine-kinase receptor c-KIT. In this review, I will summarize our recent studies demonstrating that the expression of both genes is regulated by the AP-2 transcription factor. Moreover, we have observed a loss of AP-2 expression in metastatic melanoma cells. Re-expression of AP-2 in the highly metastatic A375SM cells decreased their tumorigenicity and inhibited their metastatic potential in nude mice. MCAM/MUC18 mRNA and protein expression was significantly down-regulated while c-KIT expression was up-regulated in the AP-2-transfected cells. To further investigate the role of AP-2 in the progression of human melanoma, we attempted to inactivate AP-2 in primary cutaneous melanoma by using a dominant-negative AP-2, or the AP-2B gene. Expression of AP-2B in SB-2 cells augmented their tumorigenicity in nude mice, and upregulated MMP-2 expression and activity. As AP-2 also regulates other genes that are involved in the progression of human melanoma such as E-cadherin, p21/WAF-1, HER2/neu, Bcl-2, FAS/APO-1, IGF-R-1, VEGF and the thrombin receptor (PAR-1), we therefore propose that loss of AP-2 is a crucial event in the development of malignant melanoma. In addition, the transition of melanoma cells from RGP to VGP is also associated with over-expression of the transcription factors CREB and ATF-1. The notion that the balance between AP-2 and CREB/ATF-1 expression determines the progression of melanoma cells towards the metastatic phenotype will be discussed.
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PMID:Gene regulation in melanoma progression by the AP-2 transcription factor. 1131 Jul 95

The adhesion molecule CEACAM1 (CD66a, BGP, C-CAM) is not only involved in maintaining normal tissue architecture, but also acts as a tumor suppressor in several experimental systems where loss of CEACAM1 expression results in enhanced tumor-cell growth and tumorigenicity. In order to further analyze the role of CEACAM1 in the development of breast cancer, we performed Western-blot analysis and immunohistochemistry with highly specific monoclonal antibodies in a cohort of 68 mammary carcinomas which had also been analyzed for expression of cell-cycle regulatory proteins cyclin D1, cyclin E, p16, p21, p27, Rb, and Rb2, as well as for steroid hormone receptor status, Ki67, and HER2/neu immunoreactivity. High CEACAM1 protein expression as found using both methods correlated significantly with expression of the retinoblastoma proteins Rb (P=0.004 and 0.013) and Rb2/p130 (P=0.003 and 0.007). In addition, we found a weak association of CEACAM1 expression with p27 protein levels (P=0.087 and 0.039), but with none of the other analyzed parameters. These results indicate the possibility of a functional link between cell-adhesion molecules and cell-cycle regulation that might play an important role in the development of mammary carcinomas.
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PMID:Expression of the adhesion molecule CEACAM1 (CD66a, BGP, C-CAM) in breast cancer is associated with the expression of the tumor-suppressor genes Rb, Rb2, and p27. 1196 43