Toward gene therapy of endometriosis: adenovirus-mediated delivery of dominant negative estrogen receptor genes inhibits cell proliferation, reduces cytokine production, and induces apoptosis of endometriotic cells.

Abstract

OBJECTIVE:

To use dominant negative mutants of estrogen receptor genes delivered to endometriosis cells via an adenovirus vector (Ad-DN-ER) to abrogate estrogen action on these cells.

DESIGN:

Experimental in vitro study.

SETTING:

University research laboratory.

PATIENT(S):

Patients with ovarian endometriomas provided endometriotic cells, and patients with uterine prolapse or subserous leiomyoma provided control endometrial cells.

INTERVENTION(S):

Transfection of endometriotic cells by dominant negative estrogen receptor genes via adenovirus vector (Ad-DN-ER).

MAIN OUTCOME MEASURE(S):

The main outcome measures were cellular proliferation, cytokine production, and induction of apoptosis in endometriotic cells.

RESULT(S):

Coxsackievirus-adenovirus receptor mRNA expression and adenovirus transduction efficiency were significantly higher in endometriotic than normal endometrial cells. Ad-DN-ER-treated endometriotic cells, as compared with control virus-treated cells, showed cell rounding and detachment (cell death), a 72% reduction in the number of viable cells 5 days after transduction, significantly less production of monocyte chemotactic protein-1 (7.8 +/- 0.5 vs. 152.8 +/- 1.9 pg/mL, respectively), vascular endothelial growth factor (356.2 +/- 11.6 vs. 997.3 +/- 16.5 pg/mL, respectively), and interleukin-6 (268.7 +/- 2.6 vs. 414.5 +/- 3.6 pg/mL, respectively), and a significantly higher percentage of apoptotic cells (51.2 +/- 7.8 vs. 23.8 +/- 1.7, respectively).

CONCLUSION(S):

An adenovirus can effectively transfect endometriotic cells in vitro. The DN-ER delivered to endometriotic cells via an adenovirus decreases cell proliferation, induces apoptosis, and decreases cytokine production. Adenovirus-mediated gene therapy may represent a potential therapeutic option for endometriosis in the future.

• Authors: Essam-Eldin R Othman, Salama Salama, Nahed Ismail, Ayman Al-Hendy
• Journal: Fertility and sterility (Fertil Steril) Vol. 88 Issue 2 Pg. 462-71 (Aug 2007) ISSN: 1556-5653 [Electronic] United States
• PMID: 17343855 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CLMP protein, human
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Cytokines
• Mutant Proteins
• Receptors, Estrogen
• Receptors, Virus

Topics

• Adenoviridae (genetics)
• Apoptosis (genetics)
• Cell Proliferation
• Cells, Cultured
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Cytokines (biosynthesis)
• Endometriosis (genetics, metabolism, pathology, therapy)
• Female
• Gene Expression
• Genetic Therapy (methods)
• Genetic Vectors (pharmacology)
• Humans
• Mutant Proteins (physiology)
• Receptors, Estrogen (genetics, physiology)
• Receptors, Virus (genetics)
• Transfection