Epiregulin
A NOVEL EPIDERMAL GROWTH FACTOR WITH MITOGENIC ACTIVITY FOR RAT PRIMARY HEPATOCYTES (*)
- Hitoshi Toyoda,
- Toshi Komurasaki(§),
- Daisuke Uchida,
- Yasuko Takayama,
- Toshiaki Isobe (1),
- Tuneo Okuyama (1) and
- Kazunori Hanada
- From the Department of Applied Biology, Research Center, Taisho Pharmaceutical Co., Ltd., 1-403, Yoshino-cho, Ohmiya, Saitama 330, Japan Department of Chemistry, Faculty of Science, Tokyo Metropolitan University, Hachioji-shi, Tokyo 192-03, Japan
- § To whom correspondence should be addressed. Tel.: 81-48-663-1111; Fax: 81-48-652-7254.
Abstract
Epiregulin, a novel epidermal growth factor (EGF)-related growth regulating peptide, was purified from conditioned medium of the mouse fibroblast-derived tumor cell line NIH3T3/clone T7. It was a 46-amino-acid single chain polypeptide, and its amino acid sequence exhibited 24-50% amino acid sequence identity with sequences of other EGF-related growth factors. Epiregulin exhibited bifunctional regulatory properties: it inhibited the growth of several epithelial tumor cells and stimulated the growth of fibroblasts and various other types of cells. Epiregulin bound to the EGF receptors of epidermoid carcinoma A431 cells much more weakly than did EGF, but was nevertheless much more potent than EGF as a mitogen for rat primary hepatocytes and Balb/c 3T3 A31 fibroblasts. These findings suggest that epiregulin plays important roles in regulating the growth of epithelial cells and fibroblasts by binding to receptors for EGF-related ligands.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- EGF
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epidermal growth factor
- TGF-α
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transforming growth factor-α
- PAGE
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polyacrylamide gel electrophoresis
- HPLC
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high performance liquid chromatography
- FBS
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fetal bovine serum
- RP
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reverse phase
- cpm
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counts/min.
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↵2 D. Uchida, S. Funakoshi, N. Fujii, H. Toyoda, and T. Komurasaki, manuscript in preparation.
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↵3 H. Toyoda and T. Komurasaki, unpublished data.
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- Received November 1, 1994.
- Revision received January 1, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
