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HMGA2 and p14Arf: major roles in cellular senescence of fibroids and therapeutic implications

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Aim: To address the influence of genes involved in stem cell self-renewal and senescence on the growth of leiomyoma cells in vitro and to explore possible therapeutic implications of a targeted disruption of the p53-murine double minute 2 (MDM2) interaction. Materials and Methods: Gene expression st...

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Main Authors: Markowski, Dominique Nadine (Author) , Helmke, Burkhard Maria (Author) , Belge, Gazanfer (Author) , Nimzyk, Rolf (Author) , Bartnitzke, Sabine (Author) , Deichert, Ulrich (Author) , Bullerdiek, Jörn (Author)
Format: Article (Journal)
Language:English
Published: April 15, 2011
In: Anticancer research
Year: 2011, Volume: 31, Issue: 3, Pages: 753-761
ISSN:1791-7530
Online Access:Verlag, lizenzpflichtig, Volltext: https://ar.iiarjournals.org/content/31/3/753
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Author Notes:Dominique Nadine Markowski, Burkhard Maria Helmke, Gazanfer Belge, Rolf Nimzyk, Sabine Bartnitzke, Ulrich Deichert and Jörn Bullerdiek
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Summary:Aim: To address the influence of genes involved in stem cell self-renewal and senescence on the growth of leiomyoma cells in vitro and to explore possible therapeutic implications of a targeted disruption of the p53-murine double minute 2 (MDM2) interaction. Materials and Methods: Gene expression studies (qRT-PCR) of fibroid tissue and cells; β-galactosidase stain and qRT-PCR after antagonizing MDM2. Results: In fibroid cells, expression of HMGA2 decreased with passaging while that of p14Arf increased. Expression of these markers significantly positively, and negatively, respectively, influenced proliferation. Administration of nutlin-3, an MDM2 antagonist, induced cellular senescence and increased the expression of BAX. This, along with a significant correlation between p14Arf and BAX expression in native fibroids, suggests that p14Arf triggers senescence as well as apoptosis. Conclusion: p14Arf and HMGA2 seem to play a pivotal role in controlling the growth of fibroid cells. Antagonizing MDM2 induces senescence, as well as apoptosis, and may offer a chance to treat fibroids.
Item Description:Gesehen am 10.08.2022
Im Titel ist der Ausdruck "Arf" hochgestellt
Physical Description:Online Resource
ISSN:1791-7530

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