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 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 induces senescence, as well as apoptosis, and may offer a chance to treat fibroids.
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 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 induces senescence, as well as apoptosis, and may offer a chance to treat fibroids.
Authors: Gary Levy; Micah J Hill; Stephanie Beall; Shvetha M Zarek; James H Segars; William H Catherino Journal: J Assist Reprod Genet Date: 2012-05-15 Impact factor: 3.412
Authors: Narine M Tonoyan; Vitaliy V Chagovets; Natalia L Starodubtseva; Alisa O Tokareva; Konstantin Chingin; Irena F Kozachenko; Leyla V Adamyan; Vladimir E Frankevich Journal: Sci Rep Date: 2021-06-01 Impact factor: 4.379
Authors: Andrea Ciavattini; Jacopo Di Giuseppe; Piergiorgio Stortoni; Nina Montik; Stefano R Giannubilo; Pietro Litta; Md Soriful Islam; Andrea L Tranquilli; Fernando M Reis; Pasquapina Ciarmela Journal: Obstet Gynecol Int Date: 2013-09-12