HMGA2 and p14Arf: Major Roles in Cellular Senescence of Fibroids and Therapeutic Implications

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; beta-galactosidase stain and qRT-PCR after antagonizing MDM2. Results: In fibroid cells, expression of HMGA2 decreased with passaging while that of p14(Arf) 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 p14(Arf) and BAX expression in native fibroids, suggests that p14(Arf) triggers senescence as well as apoptosis. Conclusion: p14(Arf) and HMGA2 seem to play a pivotal role in: controlling the growth of fibroid cells. Antagonizing MDM2 in:duces senescence, as well as apoptosis, and may offer a chance to treat fibroids.