量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
Thank you very much for using our website. On the 11th of March 2019, this site was moved from our own network server to the JAIRO Cloud network server. If you previously bookmarked this site, that bookmark will no longer work. We would be grateful if you could bookmark the website again. Thank you very much for your understanding and cooperation.
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.
Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas
