Department of Cell Biology, Southern Medical University,Department of Urology, Guangzhou General Hospital of Guangzhou Military Command,Department of Cell Biology, Southern Medical University,Department of Cell Biology, Southern Medical University,Department of Cell Biology, Southern Medical University,Department of Cell Biology, Southern Medical University,1.Department of Urology, Guangzhou General Hospital of Guangzhou Military Command 2.Guangzhou Huabo Bio-pharmaceutical Research Institute
This work was supported by grants from The National Natural Science Foundation of China (81302230, 31371186), The Natural Science Foundation of Guangdong Province(2014A030313296) and Guangdong Province Outstanding Young Teacher Training Funds
The mammalian target of rapamycin(mTOR) is a serine/threonine kinase that regulates cell growth and proliferation, which plays a significant role in the pathogenesis and progression of tumors, including adrenal tumors. Numerous studies have shown that the phosphorylation levels of Akt, mTOR, S6K1 and 4EB-P1, are obviously higher in adrenocortical carcinoma(ACC) and pheochromocytomas(PCC) than in normal adrenal glands, which suggest that PI3K/Akt/mTOR signal pathway is active in adrenal tumors and probably associated with the malignant biological properties. This pathway in adrenal gland can be activated by several factors, including the loss of heterozygosity of IGF2 gene, the germline mutation in PTEN gene and the abnormal expression of microRNA, resulting in the increasing expression of VEGF and cyclin D1, which will promote proliferation, apoptosis resistance, invasion and metastasis of tumors. At present, the treatment of ACC and PCC with mTOR inhibitors has shown satisfactory effect in vitro and in vivo. What's more, a combination of mTOR inhibitors and other anti-cancer drugs provide superior effectiveness, giving new hopes to patients suffering from adrenal tumors. This review summarizes recent advances in understanding the roles of mTOR signal pathway in the pathogenesis and progression of adrenal tumors.
XU Mei-Nian, HU Wei-Lie, AO Chun-Ping, WU Yu-Kun, BAI Xiao-Chun, LIU Jun, LI Ming. Recent Advances on The Roles of mTOR Signal Pathway in The Pathogenesis and Progression of Adrenal Tumors[J]. Progress in Biochemistry and Biophysics,2016,43(3):209-218
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