Gene therapy of uterine leiomyomas: adenovirus-mediated expression of dominant negative estrogen receptor inhibits tumor growth in nude mice.
BACKGROUND
Leiomyomas (fibroids) are common estrogen-dependent uterine tumors with no effective medicinal treatment; hysterectomy is the mainstay of management.


METHODS
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).


CONCLUSIONS
Dominant-negative estrogen receptor gene therapy may provide a nonsurgical treatment option for women with symptomatic uterine fibroids who want to preserve their uteri.
Al-Hendy
Ayman
A
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Tex, USA. ayalhend@utmb.edu
Lee
Eun J
EJ
Wang
Hui Q
HQ
Copland
John A
JA
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D011960:Receptors, Estrogen / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*
D011960:Receptors, Estrogen