Estrogen receptor alpha-36 (ER-α36): A new player in human breast cancer.
Prevailing wisdom is that estrogen receptor (ER)-α mediated genomic estrogen signaling is responsible for estrogen-stimulated cell proliferation and development of ER-positive breast cancer. However, accumulating evidence indicates that another estrogen signaling pathway, non-genomic or rapid estrogen signaling, also plays an important role in mitogenic estrogen signaling. Previously, our laboratory cloned a 36 kDa variant of ER-α, ER-α36, and found that ER-α36 is mainly expressed in the cytoplasm and at the plasma membrane. ER-α36 mediates rapid estrogen signaling and inhibits genomic estrogen signaling. In this review, we review and update the biological function of ER-α36 in ER-positive and -negative breast cancer, breast cancer stem/progenitor cells and tamoxifen resistance, potential interaction and cross-talk of ER-α36 with other ERs and growth factor receptors, and intracellular pathways of ER-α36-mediated rapid estrogen signaling. The potential function and underlying mechanism of ER-α in development of ER-positive breast cancer will also be discussed.
Department of Medical Microbiology & Immunology, Creighton University Medical School, 2500 California Plaza, Omaha, NE 68178, USA. Electronic address: zywang@creighton.edu.
Zhao-Yi
ZY
Wang
Department of Medical Microbiology & Immunology, Creighton University Medical School, 2500 California Plaza, Omaha, NE 68178, USA.
Li
L
Yin
D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000627:therapeutic use
D047628:Estrogen Receptor alpha; D004967:Estrogens; C000601334:estrogen receptor alpha 36, human; D013629:Tamoxifen
Antiestrogen resistance; Breast cancer stem/progenitor cells; ER-positive and -negative breast cancer; ER-α36; Rapid estrogen signaling