Background: Amphiregulin (AR) is a novel gene of the epidermal growth factor (EGF) family. The authors have already reported that AR mRNA was expressed by human gastric carcinoma cells at various degrees, and its expression was induced by the treatment with EGF or transforming growth factor-alpha (TGF-alpha).
Methods: To elucidate the biologic role of AR in the stomach carcinogenesis, the effect of AR on the cell growth and the expression of growth factor/receptor genes in TMK-1 and MKN-28 gastric carcinoma cell lines was examined. Furthermore, to determine whether AR acts as an autocrine growth factor for gastric carcinoma cells, the authors introduced an antisense phosphorothioate oligodeoxynucleotide (S-oligo) against AR mRNA to these two cell lines.
Results: AR stimulated the growth of TMK-1 and MKN-28 cells in a dose dependent manner. The growth-promoting effect of AR was as potent as that of EGF or TGF-alpha. AR antisense S-oligo induced significant growth inhibition of both TMK-1 and MKN-28 cells compared with the control random S-oligo. Moreover, AR induced mRNA expression for AR itself, TGF-alpha, and EGF receptor in both cell lines.
Conclusions: These results overall suggest that AR acts as an autocrine growth factor for these two gastric carcinoma cell lines and evokes the cascade induction of EGF and the TGF-alpha/receptor system.