Response of the ABCG2 promoter in T47D cells and BeWo cells to sex hormone treatment.
The aim of this study was to elucidate the effects of sex hormones on activity of the ABCG2 promoter in different cell lines. T47D cells and BeWo cells were used as models for ABCG2-expressing cell lines, and luciferase assays using ABCG2 promoter-luciferase constructs were performed. It was shown that progesterone increased the response of the ABCG2 promoter in T47D cells but not in BeWo cells. On the other hand, estradiol had no effect on response of the ABCG2 promoter in either cell line. However, response of the ABCG2 promoter was enhanced by overexpression of ERalpha in both T47D cells and BeWo cells. T47D cells had higher sensitivity to ERalpha than did BeWo cells. Furthermore, it was shown that the inductive effect of progesterone on the ABCG2 promoter was inhibited by addition of RU486 or mithramycin A. Therefore, it was thought that the ABCG2 promoter responded to stimulation of the progesterone receptor (PR)-Sp1 pathway in T47D cells. Furthermore, progesterone suppressed the response of the ABCG2 promoter by changing the expression levels of PR-A and PR-B in BeWo cells. These findings suggested that there are differences between cell lines in the regulation mechanism of ABCG2 expression by sex hormone treatment.
Yasuda
Satoru
S
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo, Japan.
Kobayashi
Masaki
M
Itagaki
Shirou
S
Hirano
Takeshi
T
Iseki
Ken
K
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics*; D008926:Plicamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011980:Receptors, Progesterone / Q000378:metabolism; D013997:Time Factors
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; C066851:mithramycin A; D008926:Plicamycin