Korean J Obstet Gynecol.  2005 Jun;48(6):1431-1447.

Expression and biologic significance of human estrogen receptor-alpha and -beta, progesterone receptor A and B, androgen receptor in benign, borderline, and malignant epithelial ovarian tumors

• Lee JH
• Kim KT

Abstract

OBJECTIVE
The object of this study was to provide a better understanding of the roles played by sex hormones in ovarian carcinogenesis.
METHODS
1) The expressions of estrogen receptor-alpha and -beta, progesterone receptor A and B, androgen receptor in normal ovarian tissue, benign, borderline, and malignant ovarian tumor were analyzed using immunohistochemical stains. 2) Expression of mRNA of sex hormone receptors of cell lines from postmenopausal normal surface epithelial cells, ovarian cancer, and breast cancer were studied using real time quantitative PCR methods. 3) Expression of PR isoforms after treatment with estradiol, expression of AR after treatment with testosterone were analyzed using RT-PCR and immunoblotting methods. 4) Apoptosis after treatment with levonorgestrel in cell lines from ovarian cancer were analyzed using flowcytometry.
RESULTS
There was no significant difference in results shown by immunohistochemical staining between sex hormonal receptors of normal ovarian tissue (n=8), benign tumor (n=10), borderline tumor (n=8) and malignant tumor (n=24) according to malignant change. But, PRA was significantly reduced in epithelial ovarian cancer. 1) Expressions of ER-alpha and ER-beta, PRA, PRB and AR mRNA were seen in normal ovarian epithelial cells. 2) Deletion of exons of ER-alpha, ER-alpha wild type and variant, ER-beta variant were seen in many cell lines. 3) Down regulation of PR mRNA isoforms (especially PRA) in cell lines of ovarian cancer. 4) Flowcytometry showed that apoptotic cells markedly increased during exposure of progestins in ovarian cancer cell lines.
CONCLUSION
These results suggest that down-regulation of ER-alpha and PRA is associated with the development of ovarian epithelial carcinoma. Progestins can activate the apoptotic pathway in the ovarian epithelium for protection of normal tissue from neoplastic transformation suggests that progestins deserve further evaluation as potential ovarian cancer preventive agents.

Keyword

Estrogen receptor; Progesterone receptor; Androgen receptor; Ovarian tumors

MeSH Terms

Apoptosis
Breast Neoplasms
Carcinogenesis
Cell Line
Coloring Agents
Down-Regulation
Epithelial Cells
Epithelium
Estradiol
Estrogens*
Exons
Gonadal Steroid Hormones
Humans*
Immunoblotting
Levonorgestrel
Ovarian Neoplasms
Polymerase Chain Reaction
Progesterone*
Progestins
Protein Isoforms
Receptors, Androgen*
Receptors, Progesterone*
RNA Isoforms
RNA, Messenger
Testosterone
Coloring Agents
Estradiol
Estrogens
Gonadal Steroid Hormones
Levonorgestrel
Progesterone
Progestins
Protein Isoforms
RNA Isoforms
RNA, Messenger
Receptors, Androgen
Receptors, Progesterone
Testosterone