Development of a human epidermal growth factor derivative with EGFR-blocking and depleted biological activities: A comparative in vitro study using EGFR-positive breast cancer cells

International Journal of Biological Macromolecules
Masomeh MehrabiReza Khodarahmi

Abstract

Epidermal growth factor (EGF) is a local growth factor that stimulates cell growth, proliferation, and differentiation by binding to its receptor EGFR. EGF and EGFR are involved in many aspects of the development of carcinomas. Because EGFR has been found to be over-expressed in many tumors of epithelial origin, it is a potential target for antitumor therapy. In this study we designed a mutated form of hEGF (mEGF) with a deletion of four amino acids residues (Gln(43), Tyr(44), Arg(45) and Asp(46)) in order to show importance of Leu spatial location for EGFR binding/activation. Expression vector pET32a(+) and E. Coli, strain Rosetta-gami B (DE3) were used to enhance solubility of the recombinant protein with yielding approximately 10mg/l of cell culture. The purified cleaved hEGF as well as non-cleaved fusion protein were biologically active, which was confirmed by their equal ability to stimulate proliferation of MCF7 cells. The mEGF showed specificity and high affinity for EGFR binding, however binding affinity of mEGF for EGFR was reduced about 11.5 fold compared with that of hEGF. The mEGF effect on the MCF7 cell proliferation had a relatively different outcome; mEGF simulated differential cell growth in a dose dependent man...Continue Reading

Citations

Apr 2, 2019·Physical Chemistry Chemical Physics : PCCP·Qiang Shao, Weiliang Zhu
Sep 13, 2018·Anti-cancer Agents in Medicinal Chemistry·Baishakhi DeLuciana Scotti
Dec 31, 2020·Biomolecules·Vera UlyanovaOlga Ilinskaya
Jan 11, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Bon Il KooYoon Sung Nam

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