Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, we cloned and characterized a novel actin-binding molecule, designated skeletrophin, from aggregated neuroblastoma cells. The putative amino acid sequence of human skeletrophin cDNA contained a cysteine-rich zinc-finger motif which was also found in dystrophin and five ankyrin repeats. Northern blot analysis revealed that the 3.2-kb skeletrophin mRNA was expressed in normal skeletal muscle, and to a lesser extent in heart, brain, and kidney. Specific antibody was prepared to human skeletrophin peptide, and a single protein band with an approximate molecular weight of 70 kd was detected in tissue extracts by immunoblotting using the antibody. To better understand the biological properties of skeletrophin, we used a yeast two-hybrid system to screen for molecules interacting with skeletrophin and found that skeletrophin bound to actin monomer. Co-immunoprecipitation experiments also demonstrated that skeletrophin was able to bind to actin monomer. Fluorescence in situ hybridization mapped the skeletrophin gene on human chromosome 1p36.2-36.3, in which putative tumor suppressor genes for malignant melanoma have been postulated to exist. We therefore immunohistochemically stained benign nevi and malignant melanoma tissues. Notably, 23 of 25 benign nevi expressed skeletrophin in cytoplasm, but 18 of 38 cases of primary skin melanoma appeared to lack skeletrophin expression. Treatment with a demethylating agent, 5'-aza-2-deoxycytidine, restored skeletrophin expression in cultured Mewo melanoma cells. The present findings suggest that skeletrophin may be a novel actin-binding cytoskeleton-related molecule, expression of which is silenced in a considerable number of melanoma specimens.
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PMID:Down-regulation of a novel actin-binding molecule, skeletrophin, in malignant melanoma. 1450 47

Overexpression of various members of the Eph receptor tyrosine kinases and their ephrin ligands has been frequently reported in cancer. In contrast, a loss of EphB6 gene expression has been correlated with a poor prognosis in human neuroblastoma, suggesting a distinct role for this receptor compared to other family members. More recently, an important role of EphB6 signalling in T-cells has been described, suggesting possibly deleterious immunologic effects of a loss of EphB6 in cancer progression. We investigated the expression of EphB6 in melanocytic tumors. EphB6 mRNA of 22 microdissected tissues (7 benign nevi, 7 melanomas, 8 metastases) and 10 different cell lines (normal melanocytes, non-metastatic/metastatic melanoma cell lines) were measured by quantitative real-time RT-PCR. For visualization of EphB6 protein expression, immunohistochemistry of 32 melanocytic lesions were performed. On the mRNA level, the benign nevi revealed the highest EphB6 expression (mean = 1.43), while melanomas (mean = 0.63) and metastases (mean = 0.08; p=0.001) displayed a progressive and significant reduction of EphB6 expression. Accordingly, established melanoma cell lines with metastatic potential showed low EphB6 expression in comparison to normal melanocytes and to most of the melanoma cell lines. Immunohistochemistry revealed homogeneous staining in common nevi, whereas in malignant melanomas and metastases a heterogeneously positive to completely negative EphB6 staining was observed. Remarkably, Spitz nevi stained similarly to ordinary melanocytic nevi. Taken together, we show that melanoma progression to metastatic disease is associated with a significant reduction of EphB6 gene expression which may have considerable consequences for the prognosis of malignant melanoma patients and possible gene-therapeutic approaches.
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PMID:Loss of EphB6 expression in metastatic melanoma. 1461 26