17 beta-estradiol mimics ligand activity of the c-erbB2 protooncogene product.
We report here the physical and functional interaction of estrogen with the ErbB2 protein p185c-erbB2. The ErbB2 protein immunoprecipitated from estrogen-treated [10(-8) to 10(-6) M 17 beta-estradiol (E2)] RC cells showed higher autophosphorylation activity than that from untreated cells. Likewise autophosphorylation activity of ErbB2 protein from untreated cells was stimulated in vitro by E2. In addition, E2 treatment induced down-regulation of ErbB2 protein from the detergent-soluble fraction of the RC cells within 15 min. E2 also induced morphological transformation of the RC cells but not of the parental NIH 3T3 cells, which express little c-erbB2 under the same experimental conditions. This morphological transformation of RC cells was reversed by tamoxifen. However, E2 treatment did not induce anchorage-independent growth of RC cells. Scatchard analysis revealed E2 binding to the ErbB2 protein on RC cells; the Kd value was 2.7 nM. E2 did not bind appreciably to the parental NIH 3T3 cells or cells expressing an ErbB2 protein lacking most of its extracellular domain. These data suggest that estrogen plays an important role in ErbB2-mediated signaling.
Matsuda
S
S
Institute of Medical Science, University of Tokyo, Japan.
Kadowaki
Y
Y
Ichino
M
M
Akiyama
T
T
Toyoshima
K
K
Yamamoto
T
T
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015536:Down-Regulation; D004789:Enzyme Activation; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases; D013329:Structure-Activity Relationship
D004958:Estradiol; D004967:Estrogens; D008024:Ligands; D009856:Oncogene Proteins, Viral; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases