Estrogen receptor DNA binding is not required for estrogen-induced breast cell growth.
In this study, we determined whether ER DNA binding is necessary for estrogen to stimulate the growth of breast cancer cells. To investigate the requirement of ER DNA binding we expressed either wild-type or a DNA-binding mutant ERalpha in a clone of the MCF-7 breast cancer cell line that no longer expressed endogenous ERalpha. Estrogen did not activate non-genomic kinase cascades in the parental MCF-7 cells or in cells expressing ERalpha mutant. In cells expressing the ERalpha mutant, estrogen did not induce ERE-dependent gene expression but did induce AP-1- and Sp1-dependent gene expression and the cell cycle regulatory genes cyclin D1 and c-myc. However, we demonstrated that estrogen still induced cell proliferation in MCF-7 cells expressing the ERalpha mutant. These results demonstrate that ER DNA binding is not absolutely required for estrogen to induce breast cancer cell growth.
DeNardo
David G
DG
Department of Molecular and Cellular Biology, and Breast Center, Baylor College of Medicine, Houston, TX, USA.
Cuba
Valerie L
VL
Kim
HeeTae
H
Wu
Kendall
K
Lee
Adrian V
AV
Brown
Powel H
PH
D001940:Breast / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D016335:Zinc Fingers