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

Survivin, a novel inhibitor of apoptosis, is expressed in a variety of human cancers, with reports of prognostic significance in some neoplasms. The authors' aim was to evaluate survivin expression in a spectrum of breast lesions to determine differential expression in malignant versus benign lesions and its potential role as a diagnostic or prognostic marker. The authors found that survivin is expressed in breast tissue in the full spectrum of normal to invasive carcinoma. It is predominantly nuclear with a faint cytoplasmic blush. Survivin expression was independent of patient age and tumor size. Benign breast tissue showed survivin expression in a lower percentage of cells (45%) than malignant lesions. The median values for the percentage of cells that stained for survivin were statistically different among the categories of invasive carcinoma, DCIS, LCIS, and benign breast tissue (P < or = 0.001). The highest percentage of positive-staining cells was seen in high-grade DCIS (95%). The authors found a trend toward a higher percentage of cells staining for survivin in breast carcinoma cases that were ER negative, PR negative, or Her2/neu positive, although this was not statistically significant. Survivin expression was preserved in biopsies from recurrent tumors without loss of nuclear survivin expression. In conclusion, survivin is overexpressed in malignant breast lesions relative to benign lesions or normal breast tissue and in high-grade DCIS relative to nonhigh-grade DCIS. Therefore, survivin may have a role, albeit a limited one, as a prognostic marker in breast lesions.
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PMID:Analysis of survivin expression in a spectrum of benign to malignant lesions of the breast. 1553 28

Survivin is a member of the inhibitor of apoptosis protein family and has an essential role in mitosis. Survivin is overexpressed in a large variety of human cancers and represents an attractive target for cancer therapy. Epidermal growth factor receptor and Her/neu-transformed human tumors in particular exhibit high levels of survivin. The survivin protein forms dimers through a conserved region that is critical for subcellular localization and biological functions of the protein. We identified small molecules that target a specific cavity adjacent to the survivin dimerization surfaces. S12, a lead compound identified in the screen, can bind to the survivin protein at the intended target site. Moreover, S12 alters spindle formation, causing mitotic arrest and cell death, and inhibits tumor growth in vitro and in vivo. Cell death occurs in premetaphase stage following mitotic arrest and is not a consequence of general toxicity. Thus, the study validates a novel therapeutic target site in the survivin protein and provides a promising strategy to develop a new class of therapeutic small molecules for the treatment of human cancers.
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PMID:Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of survivin. 2189 10