乳腺発がんに重要な遺伝子同定の試み(受賞論文, 平成20年度名古屋市立大学医学会賞)
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Carcinogen exposure induces many gene expression changes in either target or non-target organ, some of them may be important for carcinogenic process but others not. In this study, we attempt to find crucial genes which may be important for mammary carcinogenesis. For this purpose, we used human c-Ha-ras proto-oncogene transgenic rats (Hras128) which are highly sensitive for mammary carcinogens, N-methy1-N-nitrosourea (MNU),7,12-dimethy1 benz [a] anthracene (DMBA) and 2-amino-1-methy1-6-phenylimidazo [4,5-b] pyridine (PhIP). We found Gpx2 as an up-regulated gene commonly in all mammary carcinomas induced the different three carcinogens by DNA microarray analysis, and its up-regulation was confirmed by quantitative RT-PCR. In addition, immunohistochemically highly expression of GPX2 was detected in not only rat mammary carcinomas but also human breast cancers. Knockdown of GPX2 expression by siRNA resulted in significant growth inhibition in both rat and human mammary carcinoma cell lines by p53 dependent manner. Thus, those data clearly demonstrated that GPX2 is involved in mammary carcinogenesis and cell proliferation in both rat and human, indicating that GPX2 may be a novel target of prevention and therapy for breast cancers.
- 名古屋市立大学の論文
- 2009-04-01
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