Gene therapy of uterine leiomyomas: Adenovirus-mediated expression of dominant negative estrogen receptor inhibits tumor growth in nude mice

Ayman Al-Hendy, Eun J. Lee, Hui Q. Wang, John A. Copland

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Leiomyomas (fibroids) are common estrogen-dependent uterine tumors with no effective medicinal treatment; hysterectomy is the mainstay of management. 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). 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). Dominant-negative estrogen receptor gene therapy may provide a nonsurgical treatment option for women with symptomatic uterine fibroids who want to preserve their uteri.

Original languageEnglish (US)
Pages (from-to)1621-1631
Number of pages11
JournalAmerican journal of obstetrics and gynecology
Volume191
Issue number5
DOIs
StatePublished - Nov 1 2004

Keywords

  • Dominant-negative estrogen receptor
  • Gene therapy
  • Leiomyomas

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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