Gpx2 is an overexpressed gene in rat breast cancers induced by three different chemical carcinogens.
Gene expression alterations are essential for the process of carcinogenesis. A carcinogen may have specific mechanisms for inducing tumors, which may involve inducing characteristic gene expression alterations. In this study, we attempted to identify genes crucial for mammary carcinogenesis. For this purpose, we used human c-Ha-ras proto-oncogene transgenic rats (Hras128), which are highly sensitive to mammary carcinogens including N-methyl-N-nitrosourea, 7,12-dimethyl benz[a]anthracene, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. DNA microarray analysis revealed that glutathione peroxidase 2 (Gpx2) was commonly up-regulated in the mammary carcinomas induced by the three different carcinogens, and its up-regulation was confirmed by quantitative reverse transcriptase-PCR and Western blotting analysis. In addition, expression of GPX2 was recognized in all 41 immunohistochemically examined cases of human breast cancer. Forced suppression of GPX2 expression by siRNA resulted in significant growth inhibition in both rat and human mammary carcinoma cell lines with wild-type p53 cells. Thus, these data suggested that GPX2 may be involved in mammary carcinogenesis and cell proliferation in both rats and humans, indicating that GPX2 may be a novel target for the prevention and therapy of breast cancer.
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, Japan.
Aya
A
Naiki-Ito
Makoto
M
Asamoto
Naomi
N
Hokaiwado
Satoru
S
Takahashi
Hiroko
H
Yamashita
Hiroyuki
H
Tsuda
Kumiko
K
Ogawa
Tomoyuki
T
Shirai
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000328:Adult; D000368:Aged; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D005260:Female; D020868:Gene Silencing; D011905:Genes, ras / Q000502:physiology; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000633:toxicity; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008770:Methylnitrosourea / Q000633:toxicity; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D002273:Carcinogens; D007093:Imidazoles; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C117436:GPX2 protein, human; D005979:Glutathione Peroxidase