Mammary and submandibular gland epidermal growth factor expression is reduced by calorie restriction

Calorie restriction reduces mammary mitogenesis and tumorigenesis. To test whether epidermal growth factor (EGF) levels are influenced by calorie intake, 72 four-week-old C3H/HeOu mice were separated into two groups and either fed ad libitum (group AL) or calorie-restricted at a mean 19% (group CR). Three mice from each group were evaluated when 6, 8, 10, and 12 weeks old for submandibular gland transcription of EGF and beta-actin RNA for levels of EGF protein in the submandibular gland, mammary gland, and serum and for immunohistological evidence of EGF protein within the submandibular and mammary glands. Submandibular levels of EGF RNA and protein and mammary and serum levels of EGF protein were similar between dietary groups when mice were 6 and 8 weeks old. Mean EGF:beta-actin RNA transcription in submandibular glands of 12-week-old mice were approximately 10-fold greater in AL compared to CR mice (ratio means, 1.499 versus 0.157, respectively; P < 0.01). Mean submandibular levels of EGF protein were greater in 10-week-old AL compared to CR mice (7017.4 versus 4098.5 ng/mg protein, respectively; P < 0.05) and even greater in 12-week-old AL compared to CR mice (4342.6 versus 137.9 ng/mg protein; P < 0.001). Mean mammary levels of EGF protein were greater among 12-week-old AL compared to CR mice (7.8 versus 5.0 ng/mg protein; P < 0.05). Serum levels of EGF did not differ between dietary cohorts. More anti-EGF immunoprecipitate was present in submandibular and mammary gland sections of 10- and 12-week-old AL compared to CR mice. Lowered EGF levels may contribute to the antiproliferative and antineoplastic effects of calorie restriction.