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PMID: 7902571 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

17 beta-estradiol mimics ligand activity of the c-erbB2 protooncogene product.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 22 ·1993-11-15 ·Pages 10803-7

Matsuda S, Kadowaki Y, Ichino M, Akiyama T, Toyoshima K, Yamamoto T

Abstract

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.

MeSH Terms
3T3 Cells Animals Cell Division/drug effects Cell Transformation, Neoplastic/genetics Down-Regulation Enzyme Activation Estradiol/metabolism,pharmacology Estrogens/metabolism In Vitro Techniques Ligands Mice Oncogene Proteins, Viral/metabolism Phosphoproteins/metabolism Protein Binding Protein-Tyrosine Kinases/metabolism Receptor, ErbB-2 Structure-Activity Relationship
Chemicals
Estrogens Ligands Oncogene Proteins, Viral Phosphoproteins Estradiol Protein-Tyrosine Kinases Receptor, ErbB-2
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Matsuda S
Institute of Medical Science, University of Tokyo, Japan.
Kadowaki Y
Ichino M
Akiyama T
Toyoshima K
Yamamoto T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.22.10803
Published
1993-11-15
Pages
10803-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC47866
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.90.22.10803 PMC Full Text View journal details
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