sub:provenance {
  beldoc: dce:description "Approximately 61,000 statements." ;
    dce:rights "Copyright (c) 2011-2012, Selventa. All rights reserved." ;
    dce:title "BEL Framework Large Corpus Document" ;
    pav:authoredBy sub:_4 ;
    pav:version "1.4" .
  sub:_3 prov:value "Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development1, 2, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer.  We used a mouse model for cancer initiation in humans: the animals have a conditional oncogenic K-rasV12 allele that is activated only by the enzyme Cre recombinase3, causing them to develop multiple lung adenomas (premalignant tumours) and a few lung adenocarcinomas (malignant tumours). Senescence markers previously identified in cultured cells were used to detect oncogene-induced senescence in lung sections from control mice (expressing Cre) and from K-rasV12-expressing mice (expressing Cre and activated K-rasV12). We analysed p16INK4a, an effector of in vitro oncogene-induced senescence1, and de novo markers that we identified by using DNA microarray analysis of in vitro oncogene-induced senescence (see supplementary information). These de novo markers are p15INK4b (also known as CDKN2B), Dec1 (BHLHB2) and DcR2 (TNFRSF10D). In addition, we looked for two features evident in cultured senescent cells, namely the expression of senescence-associated beta-galactosidase4 and the presence of senescence-associated heterochromatin foci5.  Staining with antibodies against p16INK4a, p15INK4b, Dec1 and DcR2 revealed abundant positive cells in adenomas, whereas adenocarcinomas were essentially negative (Fig. 1a)." ;
    prov:wasQuotedFrom pubmed:16079833 .
  sub:_4 rdfs:label "Selventa" .
  sub:assertion prov:hadPrimarySource pubmed:16079833 ;
    prov:wasDerivedFrom beldoc: , sub:_3 .
}