Gene therapy of uterine leiomyomas: Adenovirus-mediated expression of dominant negative estrogen receptor inhibits tumor growth in nude mice - 25/08/11
, Eun J. Lee, PhD b, Hui Q. Wang, PhD c, John A. Copland, PhD d
Reprint requests: Ayman Al-Hendy, MD, PhD, Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0587.Abstract |
Background |
Leiomyomas (fibroids) are common estrogen-dependent uterine tumors with no effective medicinal treatment; hysterectomy is the mainstay of management.
Study design |
This study was undertaken to investigate a potential therapy for leiomyoma; we used a mutated dominant-negative estrogen receptor gene delivered via an adenoviral vector (Ad-ER-DN).
Results |
Ad-ER-DN transduction, in both human and rat leiomyoma cell lines, induced an increase in both caspase-3 levels and BAX/Bcl-2 ratio with evident apoptosis in the TdT-mediated dUTP nick-end labeling assay. In nude mice, rat leiomyoma cells ex vivo transduced with Ad-ER-DN supported significantly smaller tumors compared with Ad-LacZ–treated cells 5 weeks after implantation. In mice treated by direct intratumor injection into preexisting lesions, Ad-ER-DN caused immediate overall arrest of tumor growth. The Ad-ER-DN–treated tumors demonstrated severely inhibited cell proliferation (BrdU index) and a marked increase in the number of apoptotic cells (TdT-mediated dUTP nick-end labeling index).
Conclusion |
Dominant-negative estrogen receptor gene therapy may provide a nonsurgical treatment option for women with symptomatic uterine fibroids who want to preserve their uteri.
Le texte complet de cet article est disponible en PDF.Key words : Leiomyomas, Gene therapy, Dominant-negative estrogen receptor
Plan
| Supported by NIH/NICHD grant No. 1 R01 HD046228-01 (A. A.-H.). |
Vol 191 - N° 5
P. 1621-1631 - novembre 2004 Retour au numéro
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