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MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism.


ABSTRACT: The MYC oncogene is frequently mutated and overexpressed in human renal cell carcinoma (RCC). However, there have been no studies on the causative role of MYC or any other oncogene in the initiation or maintenance of kidney tumorigenesis. Here, we show through a conditional transgenic mouse model that the MYC oncogene, but not the RAS oncogene, initiates and maintains RCC. Desorption electrospray ionization-mass-spectrometric imaging was used to obtain chemical maps of metabolites and lipids in the mouse RCC samples. Gene expression analysis revealed that the mouse tumors mimicked human RCC. The data suggested that MYC-induced RCC up-regulated the glutaminolytic pathway instead of the glycolytic pathway. The pharmacologic inhibition of glutamine metabolism with bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide impeded MYC-mediated RCC tumor progression. Our studies demonstrate that MYC overexpression causes RCC and points to the inhibition of glutamine metabolism as a potential therapeutic approach for the treatment of this disease.

SUBMITTER: Shroff EH 

PROVIDER: S-EPMC4450371 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism.

Shroff Emelyn H EH   Eberlin Livia S LS   Dang Vanessa M VM   Gouw Arvin M AM   Gabay Meital M   Adam Stacey J SJ   Bellovin David I DI   Tran Phuoc T PT   Philbrick William M WM   Garcia-Ocana Adolfo A   Casey Stephanie C SC   Li Yulin Y   Dang Chi V CV   Zare Richard N RN   Felsher Dean W DW  

Proceedings of the National Academy of Sciences of the United States of America 20150511 21


The MYC oncogene is frequently mutated and overexpressed in human renal cell carcinoma (RCC). However, there have been no studies on the causative role of MYC or any other oncogene in the initiation or maintenance of kidney tumorigenesis. Here, we show through a conditional transgenic mouse model that the MYC oncogene, but not the RAS oncogene, initiates and maintains RCC. Desorption electrospray ionization-mass-spectrometric imaging was used to obtain chemical maps of metabolites and lipids in  ...[more]

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