{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:42:45Z","timestamp":1791139365638,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,11,10]],"date-time":"2004-11-10T00:00:00Z","timestamp":1100044800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatoblastoma (HB) is the most frequent malignant liver tumour of childhood. Most HBs develop sporadically but their incidence is highly elevated in patients with familial adenomatous polyposis coli (FAP). These patients carry germline mutations in the adenomatous polyposis coli (<jats:italic>APC)<\/jats:italic> tumour suppressor gene. APC forms a multi\u2010protein complex involved in the <jats:italic>WNT<\/jats:italic> signalling pathway that controls the stability of \u03b2\u2010catenin, the central effector in this cascade. Whereas <jats:italic>APC<\/jats:italic> mutations are rare in sporadic HBs, a high frequency of <jats:italic>\u03b2\u2010catenin<\/jats:italic> mutations leading to overactivation of <jats:italic>WNT<\/jats:italic> signalling was previously found in these tumours. This pathway is negatively controlled by conductin (axin2), representing a further partner in this signalling complex. To investigate whether alterations in conductin may also be involved in the pathogenesis of sporadic HBs, 37 HBs and five HB cell lines were screened for mutations using single\u2010strand conformation polymorphism (SSCP) analysis, reverse transcription\u2010polymerase chain reaction (RT\u2010PCR), and direct sequencing. In two cases, larger deletions (52 and 1624 bp) leading to frameshifts were found. In addition, one HB carried a somatic point mutation. Expression analysis by competitive RT\u2010PCR in HBs revealed up\u2010regulation of <jats:italic>conductin<\/jats:italic> mRNA compared with adjacent liver samples. This mRNA overexpression resulted in increased conductin protein levels demonstrated by western blot analysis. Tumours with activating <jats:italic>\u03b2\u2010catenin<\/jats:italic> mutations revealed higher levels of <jats:italic>conductin<\/jats:italic> mRNA transcripts. This finding indicates that <jats:italic>conductin<\/jats:italic> is a direct target gene of <jats:italic>WNT<\/jats:italic> signalling in HBs, as has been demonstrated in other tissues. In summary, c<jats:italic>onductin<\/jats:italic> mutations may represent an alternative mechanism leading to activation of <jats:italic>WNT<\/jats:italic> signalling in HBs. The overexpression of <jats:italic>conductin<\/jats:italic> mRNA in HBs reflects activation of the <jats:italic>WNT<\/jats:italic> pathway because <jats:italic>conductin<\/jats:italic> represents a target gene of <jats:italic>WNT<\/jats:italic> signalling in liver tissue. Copyright \u00a9 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1662","type":"journal-article","created":{"date-parts":[[2004,11,10]],"date-time":"2004-11-10T15:04:12Z","timestamp":1100099052000},"page":"546-554","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Mutations and elevated transcriptional activity of <i>conductin<\/i> (<i>AXIN2<\/i>) in 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