The mammalian target of rapamycin (mTOR) signaling pathway in canine and feline soft tissue and bone sarcomas

• Main Authors: Hui-Chen Hsiao, 蕭慧貞
• Other Authors: Shih-Chieh Chang
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/77362136464140228137

碩士 === 國立中興大學 === 獸醫學系暨研究所 === 100 === Canine and feline soft tissue and bone origin sarcomas have highly invasive ability with high rate of recurrence and low to moderate metastatic potentiality. Owing to their invasiveness, the most common problem is the recurrence after conservative surgical treatment. Nevertheless, it is rarely curable and few treatments that are efficacious in advanced or metastatic sarcomas. In addition, it is reported that in various sarcomas, disruptions in phosphatidylinositaol 3-kinase (PI3K)-Akt-mTOR signaling pathway are associated with malignant transformation. Therefore, the blockade of this pathway represents an emerging target for therapy of sarcomas. It has demonstrated that mTOR inhibitors showed promising outcome in patients with metastatic sarcomas (Vemulapalli et al., 2011). The objective of our study is to investigate activation of mTOR signaling pathway in canine and feline soft tissue and bone origin sarcomas. In immunoblotting, 25 sarcomas were used to assess the expression of endogenous and phosphorylated Akt, mTOR, and S6K. The immunohistochemical (IHC) staining was performed in 59 tumors to aid investigating in localization and intensity of each component in the pathway. Results indicated Akt/mTOR/S6K pathway proteins were frequently expressed and activated in canine and feline sarcomas. The expression of mTOR may play a role in metastasis. Strong staining intensities of mTOR, p-S6K, and S6K were correlated with first admittance metastasis in canine sarcomas. Strong staining intensity of p-mTOR was related to grade III FISS. Further researches were needed for elucidating the complexity of mechanism. The results above have presented a promising potential of mTOR pathway proteins in canine and feline sarcomas, and opened an exciting avenue for further clinical and translational studies that will hopefully to reach the best efficacy in the treatment of canine and feline soft tissue and bone origin sarcomas.