MYC Oncogene Overexpression Drives Renal Cell Carcinoma in a Mouse Model Through Glutamine Metabolism

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2015 May 13

PMID 25964345

Citations 154

Authors

Emelyn H Shroff

Livia S Eberlin

Vanessa M Dang

Arvin M Gouw

Meital Gabay

Stacey J Adam

David I Bellovin

Phuoc T Tran

William M Philbrick

Adolfo Garcia-Ocana

Stephanie C Casey

Yulin Li

Chi V Dang

Richard N Zare

Dean W Felsher

Affiliations

Soon will be listed here.

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.

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