Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice

International Journal of Molecular Sciences

KellyA. Martin¹  GabrielaG. Loots¹  Wei He¹  Aimy Sebastian¹  NicholasR. Hum¹  Chong-xian Pan²  ParamitaM. Ghosh²  Salma Siddiqui²  Ralph de Vere White² 

[1] Lawrence Livermore National Laboratory, Physical and Life Sciences Directorate, Livermore, CA 94550, USA;UC Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA;

关键词: bladder cancer;    drug resistance;    methyltransferase;    gemcitabine;   

DOI  :  10.3390/ijms20204983

来源: DOAJ

【 摘 要 】

Bladder cancer is among the top ten most common cancers, with about ~380,000 new cases and ~150,000 deaths per year worldwide. Tumor relapse following chemotherapy treatment has long been a significant challenge towards completely curing cancer. We have utilized a patient-derived bladder cancer xenograft (PDX) platform to characterize molecular mechanisms that contribute to relapse following drug treatment in advanced bladder cancer. Transcriptomic profiling of bladder cancer xenograft tumors by RNA-sequencing analysis, before and after relapse, following a 21-day cisplatin/gemcitabine drug treatment regimen identified methionine adenosyltransferase 1a (MAT1A) as one of the significantly upregulated genes following drug treatment. Survey of patient tumor sections confirmed elevated levels of MAT1A in individuals who received chemotherapy. Overexpression of MAT1A in 5637 bladder cancer cells increased tolerance to gemcitabine and stalled cell proliferation rates, suggesting MAT1A upregulation as a potential mechanism by which bladder cancer cells persist in a quiescent state to evade chemotherapy.

【 授权许可】

Unknown