{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:29:06Z","timestamp":1791156546962,"version":"4.1.0"},"reference-count":42,"publisher":"Bioscientifica","issue":"6","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p>\n                    Phaeochromocytomas (PCCs) are benign neuroendocrine tumours of the adrenal medulla. Approximately 10% of PCC patients develop metastases, but this frequency is much higher in specific subtypes of patients. The reliable diagnosis of malignant PCC can only be made after identification of a metastasis. To study the effect of\n                    <jats:italic>Trp53<\/jats:italic>\n                    inactivation on PCC pathogenesis in\n                    <jats:italic>Pten<\/jats:italic>\n                    KO mice, we investigated the adrenals of a large cohort of mice with conditional monoallelic and biallelic inactivation of\n                    <jats:italic>Trp53<\/jats:italic>\n                    and\n                    <jats:italic>Pten<\/jats:italic>\n                    . The adrenal weights were determined for all mice, and in a proportion of these mice, immunohistochemistry for tyrosine hydroxylase and dopamine \u03b2-hydroxylase was performed on the adrenals and corresponding lungs. Finally, comparative genomic hybridization (CGH) was performed. The histological and immunohistochemical results confirmed that the adrenal tumours were PCCs. Inactivation of one or both alleles of\n                    <jats:italic>Trp53<\/jats:italic>\n                    resulted in earlier tumour occurrence in the\n                    <jats:italic>Pten<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>loxP\/loxP<\/jats:italic>\n                    <\/jats:sup>\n                    mice as well as in the\n                    <jats:italic>Pten<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>loxP\/+<\/jats:italic>\n                    <\/jats:sup>\n                    mice. In addition, lung metastases were found in up to 67% of mice. The CGH results showed that the most frequent genomic alterations were loss of chromosome 19 (86%) and gain of chromosome 15 (71%). In this study, we have shown that\n                    <jats:italic>Pten<\/jats:italic>\n                    \/\n                    <jats:italic>Trp53<\/jats:italic>\n                    KO mice showed metastatic PCC at high frequency and primary tumours occurred at younger ages in mice with\n                    <jats:italic>Trp53<\/jats:italic>\n                    inactivation. Therefore, the present model appears to be a suitable model that might allow the preclinical study of new therapeutics for these tumours.\n                  <\/jats:p>","DOI":"10.1530\/erc-12-0088","type":"journal-article","created":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T23:01:57Z","timestamp":1346194917000},"page":"731-740","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":6,"title":["Trp53 inactivation leads to earlier phaeochromocytoma formation in pten knockout mice"],"prefix":"10.1530","volume":"19","author":[{"given":"Esther","family":"Korpershoek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanne K","family":"Kloosterhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique","family":"Ziel-van der Made","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanneke","family":"Korsten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Oudijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Trapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winand N M","family":"Dinjens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald R","family":"de Krijger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"issue":"9","key":"1_35450224","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1055\/s-0029-1231025","volume":"41","author":"Adjalle","year":"2009","journal-title":"Hormone and metabolic research. 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