A cell line designated TSG6 was established from a signet-ring cell gastric
carcinoma developed in a 57-year-old female patient. The TSG6 cells had well preserved the features of
signet-ring cell carcinoma based on morphology. The cells exhibited both
epidermal growth factor (
EGF) and
epidermal growth factor receptor (EGFR) immunoreactivities, and also secreted
EGF. Moreover, the growth of TSG6 cells was stimulated in the presence of exogenous
EGF. These results suggest that the possible presence of an
EGF/EGFR autocrine growth mechanism is expressed in the TSG6 cells. The simultaneous treatment with
EGF and
5-fluorouracil (5-FU) produced a nearly 2.4-fold enhancement of
5-FU cytotoxicity against TSG6 cells. A
bromodeoxyuridine/
DNA flow cytometry analysis revealed that
EGF augmented
5-FU cytotoxicity by inducing the accumulation of S phase cells which might be more susceptible to
5-FU. Moreover, we found that the incorporation of
5-FU into the TSG6 cells was increased with the addition of
EGF. These data indicate that
EGF may be a potent agent as a
biological response modifier for
5-FU against the
tumors which express the
EGF/EGFR autocrine mechanism, and that the TSG6 cell line is useful in furthering our understanding of the interaction between anticancer drugs and
EGF.