MAMMARY AND SUBMANDIBULAR-GLAND EPIDERMAL GROWTH-FACTOR EXPRESSION ISREDUCED BY CALORIE RESTRICTION

Calorie restriction reduces mammary mitogenesis and tumorigenesis. To test whether epidermal growth factor (EGF) levels are influenced by ca lorie intake, 72 four-week-old C3H/HeOu mice mere separated into two g roups and either fed ad libltum (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 p-actin RNA for levels of EGF protein in the submandibular gland, mammary gland, and serum and for immunohistological evidence of EGF pr otein within the submandibular and mammary glands. Submandibular level s of EGF RNA and protein and mammary and serum levels of EGF protein w ere similar between dietary groups when mice were 6 and 8 weeks old. M ean EGF:beta-actin RNA transcription in submandibular glands of It-wee k-old mice were similar to 10-fold greater in AL compared to CR mice ( ratio means, 1.499 versus 0.157, respectively; P < 0.01). Mean submand ibular levers of EGF protein were greater in 10-week-old AL compared t o 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 w ere greater among 12-week-old AL compared to CR mice (7.8 versus 5.0 n g/mg protein; P < 0.05). Serum levels of EGF did not differ between di etary cohorts. More anti-EGF immunoprecipitate was present in submandi bular and mammary gland sections of 10- and 12-week-old AL compared to CR mice. Lowered EGF levels may contribute to the antiproliferative a nd antineoplastic effects of calorie restriction.