@article{oai:repo.qst.go.jp:00048144,
 author = {Showler, Kaye and Nishimura, Mayumi and Daino, Kazuhiro and Imaoka, Tatsuhiko and Nishimura, Yukiko and Morioka, Takamitsu and J., Blyth Benjamin and Kokubo, Toshiaki and Takabatake, Masaru and Fukuda, Maki and Moriyama, Hitomi and Kakinuma, Shizuko and Fukushi, Masahiro and Shimada, Yoshiya and ショウラー 恵 and 西村 まゆみ and 臺野 和広 and 今岡 達彦 and 西村 由希子 and 森岡 孝満 and Ｂｌｙｔｈ Ｂｅｎｊａｍｉｎ and 小久保 年章 and 高畠 賢 and 福田 真希 and 森山 ひとみ and 柿沼 志津子 and 島田 義也},
 issue = {2},
 journal = {Journal of radiation research},
 month = {Oct},
 note = {The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine if any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only in a minority of carcinoma cells. The negative pathway regulator Inpp4b was significantly down-regulated in both groups, compared to normal mammary tissue, and radiation-induced carcinomas also showed a significant decrease in Pten expression, while the chemical-induced carcinomas showed a decrease in Pik3r1 and Pdk1. Significant up-regulation of the positive regulators Erbb2 and Pik3ca was observed only in chemical-induced carcinomas. However, no genes showed clear correlations with AKT phosphorylation levels except in individual carcinomas. Only rare carcinomas showed mutations in PI3K/AKT pathway genes, yet these carcinomas did not exhibit stronger AKT phosphorylation. Thus, while AKT phosphorylation is a common feature of rat mammary carcinomas induced by radiation or a canonical chemical carcinogen, the mutation of key genes in the pathways or permanent changes to gene expression of particular signaling proteins do not explain the pathway activation in the advanced cancers. Although AKT signaling likely facilitates cancer development and growth in rat mammary carcinomas, it is unlikely that permanent disruption of the PI3K/AKT pathway genes is a major causal event in radiation carcinogenesis.},
 pages = {183--194},
 title = {Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas},
 volume = {58},
 year = {2016}
}