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Epidermal Growth Factor (EGF) Receptors in Human Chorionic Gonadotropin-Producing Tumor: Transplantation in Nude Mice and the Effect of EGF on Tumor Growth

First Department of Internal Medicine, Toho University School of Medicine 5–21-16 Ohmori-nishi, Ota-ku, Tokyo 143, Japan

We examined the presence and characteristics of epidermal growth factor (EGF) receptors in hCG producing tumors (CC-2-JCK) transplanted in female nude mice. We also examined the in vivo effects of EGF on tumor growth. Specific receptors with apparent dissociation constants of 3.89 x 10^–10 and 1.0 x 10^–9 M and binding capacities of 5.96 x 10^–10 and 1.52 x 10^–9 /mg protein for EGF have been identified in the hCGproducing tumor. [¹²⁵I]EGF binding to the tumor tissues was time, temperature, and tissue weight dependent and specific. EGF and transforming growth factor- (TGF) competed for [¹²⁵I]EGF binding, with 50% of the bound [¹²⁵I]EGF displaced by approximately 0.52 nM EGF and 3.10 nM TGF. TGFβ competed for [¹²⁵I]EGF binding slightly. Five micrograms of EGF caused an increase in the rate of tumor growth, while 50 µg EGF strongly inhibited tumor growth. The concentration of [¹²⁵I]EGF binding in the tumor treated with low doses of EGF was high, and that in the tumor treated with high doses of EGF was low. These changes in EGF binding were attributable to the changes in the number of high affinity EGF receptors with no significant alteration in binding affinity. In conclusion, the existence of high concentrations of EGF receptors with high affinity and specificity to EGF was demonstrated in an hCGproducing tumor transplanted in nude mice and appeared to be correlated with tumor growth.

^* To whom requests for reprints should be addressed.

Received October 30, 1989.