{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T03:51:53Z","timestamp":1778039513848,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2010,4,22]],"date-time":"2010-04-22T00:00:00Z","timestamp":1271894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathogenetically, uterine leiomyomas (ULs) can be interpreted as the result of a monoclonal abnormal proliferation of myometrial cells. Oncogene\u2010induced senescence (OIS) is a frequent phenomenon in premalignant lesions that leads to a growth arrest mainly by the activation of two potent growth\u2010inhibitory pathways as represented by p16<jats:sup>Ink4a<\/jats:sup> and p19<jats:sup>Arf<\/jats:sup>. The relevance of OIS for the development of UL has not been addressed, but HMGA2, encoded by a major target gene of recurrent chromosomal abnormalities in UL, has been implicated in the repression of the <jats:italic>Ink4a\/Arf<\/jats:italic> (<jats:italic>CDKN2A<\/jats:italic>) locus. This prompted us to examine if HMGA2 contributes to the growth of leiomyomas by repressing this locus. Contrary to the expectations, we were able to show that generally ULs express significantly higher levels of p19<jats:sup>Arf<\/jats:sup> mRNA than myometrium and that UL with 12q14\u223c15 rearrangements showed higher expression levels than UL with other cytogenetic aberrations. Furthermore, the finding of a significant correlation between the expressions of <jats:italic>p19<\/jats:italic><jats:sup><jats:italic>Arf<\/jats:italic><\/jats:sup> and <jats:italic>CDKN1A<\/jats:italic> shows that p19<jats:sup>Arf<\/jats:sup> triggers senescence rather than apoptosis in UL. Furthermore, the expression levels of <jats:italic>HMGA2<\/jats:italic>, <jats:italic>p19<\/jats:italic><jats:sup><jats:italic>Arf<\/jats:italic><\/jats:sup>, and <jats:italic>CDKN1A<\/jats:italic> were found to be correlated with the size of the tumors, indicating that an enhanced growth potential is counterbalanced by the p19<jats:sup>Arf<\/jats:sup> pathway. Mechanistically, the UL may thus execute a program already present in their cell of origin, where it is activated to protect the genome, for example, in the case of enhanced proliferation. In summary, the results identify the p19<jats:sup>Arf<\/jats:sup>\u2010TP53\u2010CDKN1A pathway as a major player in the growth control and genomic stability of uterine fibroids. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/gcc.20777","type":"journal-article","created":{"date-parts":[[2010,4,22]],"date-time":"2010-04-22T22:01:37Z","timestamp":1271973697000},"page":"661-668","source":"Crossref","is-referenced-by-count":29,"title":["HMGA2 and the p19<sup>Arf<\/sup>\u2010TP53\u2010CDKN1A axis: A delicate balance in the growth of uterine leiomyomas"],"prefix":"10.1002","volume":"49","author":[{"given":"Dominique Nadine","family":"Markowski","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga","family":"von Ahsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maliheh 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