Abstract 2474: Increased PKC expression in diacylglycerol-induced mammary carcinogenesis in the human c-Ha-ras proto-oncogene transgenic rat

Protein kinase C (PKC) is implicated in cell proliferation and tumor promotion. PKC is activated by 1, 2-diacylglycerol (1, 2-DAG). An edible oil that includes 70% 1,3-DAG and 30% 1,2-DAG is commercially available in Japan, USA, and European countries. To examine whether the DAG oil enhances mammary carcinogenesis and to measure whether DAG affects the levels of PKC expression, we carried out this study with human c-Ha-ras proto-oncogene transgenic (Hras128) rats that are highly susceptible to mammary carcinogenesis. Hras128 rats (6-week-old) were randomly assigned into four experimental groups. DAG oil was administered to the rat as oral drops. Group 1 (G1): 0.5 mL triacylglyceraol (TAG) x2/week, Group 2 (G2): 0.5 mL DAG x2/week, Group 3 (G3): 0.5 mL TAG x1/week plus 0.5 mL DAG x1/week, Group 4 (G4): 0.5 mL DAG x1/2 weeks + 0.5 mL TAG x3/2 weeks. Experiment was terminated after 15 weeks. Mammary tumors were histologically identified as adenocarcinoma. Tumor incidence of G2 (77%) and G3 (77%) was significantly higher than G1 (22%). Tumor multiplicity of G2 (1.3 ± 1.1) was significantly higher than the other 3 groups (G1, 0.4 ± 1.0; G3, 0.9 ± 0.6; G4, 0.7 ± 1.0). In tumor samples, the mRNA expression levels of 6 PKC isoforms (α, δ, e, η, λ, ν) increased compared to the adjacent normal tissues. In a parallel study, we also examined the levels of PKC expression in normal mammary tissues of Hras128 rats treated with either TAG or DAG oils alone for 4 weeks. The mRNA expression levels of 5 PKC isoforms (δ, e, η, λ, θ) significantly increased in the DAG-treated normal tissues compared to the TAG-treated normal tissues. These findings provide evidence that treatment of Hras128 rats with DAG oil may promote mammary carcinogenesis by inducing expression of several PKC isoforms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2474.