| http://purl.uniprot.org/citations/18506750 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18506750 | http://www.w3.org/2000/01/rdf-schema#comment | "We have previously localized a cervical cancer tumor suppressor gene to a 300 kb interval of 11q13. Analysis of candidate genes revealed loss of expression of cystatin E/M, a lysosomal cysteine protease inhibitor, in 6 cervical cancer cell lines and 9 of 11 primary cervical tumors. Examination of the three exons in four cervical cancer cell lines, 19 primary tumors, and 21 normal controls revealed homozygous deletion of exon 1 sequences in one tumor. Point mutations were observed in six other tumors. Two tumors contained mutations at the consensus binding sites for cathepsin L, a lysosomal protease overexpressed in cervical cancer. Introduction of these two point mutations using site directed mutagenesis resulted in reduced binding of mutated cystatin E/M to cathepsin L. Although mutations were not observed in any cell lines, four cell lines and 12 of 18 tumors contained promoter hypermethylation. Reexpression of cystatin E/M was observed after 5'aza 2-deoxycytidiene and/or Trichostatin A treatment of cervical cancer cell lines, HeLa and SiHa, confirming promoter hypermethylation. Ectopic expression of cystatin E/M in these two cell lines resulted in growth suppression. There was also suppression of soft agar colony formation by HeLa cells expressing the cystatin E/M gene. Reexpression of cystatin E/M resulted in decreased intracellular and extracellular expression of cathepsin L. Overexpression of cathepsin L resulted in increased cell growth which was inhibited by the reintroduction of cystatin E/M. We conclude, therefore, that cystatin E/M is a cervical cancer suppressor gene and that the gene is inactivated by somatic mutations and promoter hypermethylation."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.org/dc/terms/identifier | "doi:10.1002/gcc.20576"xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/author | "Lee G."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/author | "Stanbridge E.J."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/author | "Keppler D."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/author | "Mendonca M.S."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/author | "Wilczynski S.P."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/author | "Srivatsan E.S."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/author | "Redpath J.L."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/author | "Veena M.S."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/name | "Genes Chromosomes Cancer"xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/pages | "740-754"xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/title | "Inactivation of the cystatin E/M tumor suppressor gene in cervical cancer."xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://purl.uniprot.org/core/volume | "47"xsd:string |
| http://purl.uniprot.org/citations/18506750 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18506750 |
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