Augmentation of estrogen receptor-mediated transcription by steroid and xenobiotic receptor.
The estrogen receptor (ER) is a key regulator of proliferation and differentiation in breast cancer cells. In the present study, the effect of steroid and xenobiotic receptor (SXR) on 17/beta-estradiol (E2)-induced transcription through ERalpha was studied. SXR augmented ER-mediated transcription in the presence of E2 in MCF-7 breast cancer-derived cells and CV-1 fibroblast-derived cells. On the other hand, SXR alone did not affect the estrogen response element (ERE)-containing promoter activity in CV-1 cells. SXR did not directly bind to ERalpha or ERE in vitro, indicating that SXR may affect ER-mediated transcription by altering cofactor binding to ER. Although SXR did not alter the binding between ERalpha and p300/CBP interacting protein (p/CIP), it decreased the binding of a specific corepressor, silencing mediator of retinoid and thyroid hormone receptors (SMRT) to liganded ERalpha as assessed by mammalian two-hybrid, glutathione S-transferase pull-down, immunoprecipitation and newly developed Liquid Chemiluminescent DNA Pull-Down Assays. These results indicate that SXR augmented ER-mediated transcription by dissociating SMRT from ERalpha. Thus, the expression of SXR in breast cancer cells may alter the ER signaling, which may play crucial role for growth and differentiation of breast cancer cells.
Rokutanda
Nana
N
Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Iwasaki
Toshiharu
T
Odawara
Hiroki
H
Nagaoka
Rin
R
Miyazaki
Wataru
W
Takeshita
Akira
A
Koibuchi
Yukio
Y
Horiguchi
Jun
J
Shimokawa
Noriaki
N
Iino
Yuichi
Y
Morishita
Yasuo
Y
Koibuchi
Noriyuki
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D056985:Nuclear Receptor Co-Repressor 2; D000077297:Pregnane X Receptor; D011401:Promoter Regions, Genetic / Q000502:physiology; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; C539130:NCOR2 protein, human; D056985:Nuclear Receptor Co-Repressor 2; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D012097:Repressor Proteins; D004958:Estradiol