PARENT SESSION
OVARY - C

Wednesday, August 4, 2004
10:30 AM–12:30 PM
Buchanan Courtyard

(778) FUNCTIONAL AND GENOMIC CHANGES BY ESTROGEN AND ENDOCRINE DISRUPTORS IN OVARIAN CANCER CELL LINE, BG-1.

Park, Se-Hyung¹, An, Beum-Soo¹, Choi, Jung-Hye¹, Leung, Peter C. K.¹, Jeung, Eui-Bae², Choi, Kyung-Chul¹, ¹ Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada² Laboratory of Veterinary Biochemistry and Molecular Biology, Cheongju, Chungbuk, Republic of Korea

ABSTRACT- Environmental chemicals, known as endocrine disruptors, interfere with the endocrine systems and adversely effect hormone balance or disrupt normal function in the organs that hormones regulate or modulate. However, the mechanism of endocrine disruptors in reproductive system remains unclear. In a present study, we investigated the effects of estrogen (E2) and endocrine disruptors, octylphenol (OP), nonylphenol (NP), bisphenol A (BPA), and methoxychlor (MXC), on cell growth and transcriptional level of estrogen response element (ERE) in an ovarian cell line, BG-1. BG-1 cells were treated with E2 and endocrine disruptors at different times and doses, and thymidine incorporation assay was performed. To compare the mechanism of E2 and endocrine disruptors, transcriptional level of ERE was investigated in ERE-tk-Luc transfected BG-1 cells. To elucidate a change in the gene profiling by E2 and BPA, BG-1 cells were treated at different times up to 24 h, and altered gene profiles were traced and compared between two groups (E2 and BPA) by microarray analysis. Treatments with E2 (10-11 to 10-7 M) and OP, NP, BPA and MXC (10-8 to 10-5 M) for 24 h resulted in the stimulation of cell growth in BG-1 cells. Treatments with increasing doses (10-6 and 10-5 M) of OP, NP, and BPA, and a high dose of MXC (10-5 M) resulted in an increase (up to 10-fold) of ERE activity at the transcriptional level in ERE-tk-Luc transfected BG-1 cells. These stimulatory effects were completely blocked by anti-estrogen, ICI 182,780. In addition, we observed the up-regulation of gene profile involved in cell cycle progression and anti-apoptosis, such as cyclin D and survivin, and the down-regulation of transcriptional repressor, anti-proliferative, and pro-apoptotic genes such as Mad4, cyclin G, BCL2-interacting killer by microarray analysis. These results indicate that E2 and endocrine disruptors have growth stimulatory effects and their actions are mediated by ERs in the stimulation of cell growth and ERE activity at the transcriptional level in ovarian cancer BG-1 cells. Our results indicate the gene profile regulated by E2 and BPA may have a similar pattern in these cells. [This work was supported by the Canadian Institutes of Health Research and StartUp Fund from Faculty of Medicine, University of British Columbia.]

KEY WORDS: E2, ER, Microarray, Ovarian cancer, Endocrine disruption