Physiologic estrogen receptor alpha signaling in non-tumorigenic human mammary epithelial cells.
Currently, a number of breast cancer cell lines exist that serve as models for both estrogen receptor alpha (ERalpha) positive and ERalpha negative disease. Models are also available for pre-neoplastic breast epithelial cells that do not express ERalpha; however, there are no ideal systems for studying pre-neoplastic cells that are ERalpha positive. This has been largely due to the inability to establish an estrogen growth stimulated, non-tumorigenic breast epithelial cell line, as most human breast epithelial cells engineered to overexpress ERalpha have been found to be growth inhibited by estrogens. We have developed independently derived clones from the non-cancerous MCF-10A human breast cell line that express ERalpha and are growth stimulated by 17-beta-estradiol (E2) in the absence of epidermal growth factor (EGF), a cytokine normally required for MCF-10A cell proliferation. This effect is blocked by the selective estrogen receptor modulator (SERM), Tamoxifen and the selective estrogen receptor downregulator, ICI 182,780 (Faslodex, Fulvestrant). Exposure of these cells to EGF and E2 results in a growth inhibitory phenotype similar to previous reports. These data present a reconciling explanation for the previously described paradoxical effects of ERalpha overexpression, and provide a model for examining the carcinogenic effects of estrogens in non-tumorigenic human breast epithelial cells.
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abde M
AM
Abukhdeir
Brian G
BG
Blair
Keith
K
Brenner
Bedri
B
Karakas
Hiroyuki
H
Konishi
Joselin
J
Lim
Vanita
V
Sahasranaman
Yi
Y
Huang
Judith
J
Keen
Nancy
N
Davidson
Michele I
MI
Vitolo
Kurtis E
KE
Bachman
Ben Ho
BH
Park
D001940:Breast / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D010766:Phosphorylation; D011230:Precancerous Conditions; D020218:Response Elements; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013997:Time Factors
D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol