ATBF1 inhibits estrogen receptor (ER) function by selectively competing with AIB1 for binding to the ER in ER-positive breast cancer cells.
Loss of the q22 band of chromosome 16 is a frequent genetic event in breast cancer, and the candidate tumor suppressor gene, ATBF1, has been implicated in breast cancer by genomic deletion, transcriptional down-regulation, and association with better prognostic parameters. In addition, estrogen receptor (ER)-positive breast cancer expresses a higher level of ATBF1, suggesting a role of ATBF1 in ER-positive breast cancer. In this study, we examined whether and how ATBF1 affects the ER function in breast cancer cells. We found that ATBF1 inhibited ER-mediated gene transcription, cell growth, and proliferation in ER-positive breast cancer cells. In vitro and in vivo immunoprecipitation experiments revealed that ATBF1 interacted physically with the ER and that multiple domains in both ATBF1 and ER proteins mediated the interaction. Furthermore, we demonstrated that ATBF1 inhibited ER function by selectively competing with the steroid receptor coactivator AIB1 but not GRIP1 or SRC1 for binding to the ER. These findings not only support the concept that ATBF1 plays a tumor-suppressive role in breast cancer, they also provide a mechanism for how ATBF1 functions as a tumor suppressor in breast cancer.
Dong
Xue-Yuan
XY
From the Winship Cancer Institute and Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia 30322.
Sun
Xiaodong
X
From the Winship Cancer Institute and Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia 30322.
Guo
Peng
P
From the Winship Cancer Institute and Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia 30322.
Li
Qunna
Q
From the Winship Cancer Institute and Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia 30322.
Sasahara
Masakiyo
M
Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.
Ishii
Yoko
Y
Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama 930-0194, Japan.
Dong
Jin-Tang
JT
From the Winship Cancer Institute and Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia 30322. Electronic address: j.dong@emory.edu.
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C491310:GRIP1 protein, human; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011960:Receptors, Estrogen; D025521:Tumor Suppressor Proteins; C071660:ZFHX3 protein, human; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3