The TORC1/2 inhibitor TAK228 sensitizes atypical teratoid rhabdoid tumors to cisplatin-induced cytotoxicity.

ABSTRACT:

Background

Atypical teratoid/rhabdoid tumors (AT/RTs) are deadly pediatric brain tumors driven by LIN28. Mammalian target of rapamycin (mTOR) is activated in many deadly, drug-resistant cancers and governs important cellular functions such as metabolism and survival. LIN28 regulates mTOR in normal cells. We therefore hypothesized that mTOR is activated downstream of LIN28 in AT/RT, and the brain-penetrating mTOR complex 1 and 2 (mTORC1/2) kinase inhibitor TAK228 would reduce AT/RT tumorigenicity.

Methods

Activation of mTOR in AT/RT was determined by measuring pS6 and pAKT (Ser473) by immunohistochemistry on tissue microarray of 18 primary AT/RT tumors. In vitro growth assays (BrdU and MTS), death assays (CC3, c-PARP by western blot), and survival curves of AT/RT orthotopic x

SUBMITTER: Rubens JA 

PROVIDER: S-EPMC5604899 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature