Epidermal growth factor (EGF) and transforming growth factor-~ (TGF-~) are polypeptides which bind to the EGF receptor (EGFr) and may play a role in cell growth and carcinogenesis. Our study investigated the content of EGF, TGF<z, and EGFr in tumors of the stomach and the colon in comparison with th
Regulation of epidermal growth factor receptor expression in normal and transformed keratinocytes
โ Scribed by M. F. W. Pas; P. M. P. Bergen en Henegouwen; J. Boonstra; M. Ponec
- Publisher
- Springer-Verlag
- Year
- 1991
- Tongue
- English
- Weight
- 926 KB
- Volume
- 283
- Category
- Article
- ISSN
- 0340-3696
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โฆ Synopsis
Transformed keratinocytes (SCC-4, SCC-15, SCC-12F2, SVK14) or normal keratinocytes which differ in their differentiation programme were used to study the regulation of EGF-receptor expression. The capacity of the cells to differentiate was modulated by changing the extracellular calcium concentration. We were able to demonstrate that EGF-receptor expression in normal and transformed keratinocytes depends upon the cell type and one or more levels of regulatory control. At the DNA level, EGF-receptor gene amplification occurred in poorly differentiating cells. At the mRNA level, cells showing EGF-receptor gene amplification expressed elevated mRNA and protein levels when cultured under low Ca2+ conditions. Cells not exhibiting EGF-receptor gene amplification showed equal mRNA expression, regardless the Ca2+ concentration in the culture medium. At the protein level, EGF-receptor protein was decreased in cells exhibiting EGF-receptor gene amplification when extracellular Ca2+ was increased (to 1.6 mM) to stimulate differentiation, the decrease in protein being comparable to mRNA expression. Cells not exhibiting EGF-receptor gene amplification showed equal protein expression, regardless of the Ca2+ concentration in the culture medium. Under the same conditions, SV40 transformed keratinocytes showed equal mRNA but elevated protein expression in cells grown under low Ca2+ conditions. At the membrane level, normal keratinocytes and SCC-17F2 cells showed elevated numbers of cell surface exposed EGF-receptors in cells grown under low Ca2+ conditions, but equal mRNA and protein expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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Epidermal growth factor (EGF) and transforming growth factor-alpha (TGFo0 are two closely related peptides that interact with cell-surface epidermal growth factor receptors (EGFR) to induce receptor tyrosine phosphorylation and activation of intracellular signal-transduction pathways. EGF appears to