Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice
Abstract
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.
- Authors:
-
[2];
[3];
[3];
[4];
[5]
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Georgetown Univ., Washington, DC (United States)
- Univ. of California, Merced, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Univ. of California, Davis, CA (United States)
- Univ. of California, Merced, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Univ. of California, Davis, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA)
- OSTI Identifier:
- 1867541
- Alternate Identifier(s):
- OSTI ID: 1698296
- Report Number(s):
- LLNL-JRNL-811540; LLNL-JRNL-776618
Journal ID: ISSN 1422-0067; 1018414
- Grant/Contract Number:
- AC52-07NA27344
- Resource Type:
- Accepted Manuscript
- Journal Name:
- International Journal of Molecular Sciences (Online)
- Additional Journal Information:
- Journal Name: International Journal of Molecular Sciences (Online); Journal Volume: 20; Journal Issue: 20; Journal ID: ISSN 1422-0067
- Publisher:
- MDPI
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; bladder cancer; drug resistance; methyltransferase; gemcitabine
Citation Formats
Martin, Kelly A., Hum, Nicholas R., Sebastian, Aimy, He, Wei, Siddiqui, Salma, Ghosh, Paramita M., Pan, Chong-xian, de Vere White, Ralph, and Loots, Gabriela G. Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice. United States: N. p., 2019.
Web. doi:10.3390/ijms20204983.
Martin, Kelly A., Hum, Nicholas R., Sebastian, Aimy, He, Wei, Siddiqui, Salma, Ghosh, Paramita M., Pan, Chong-xian, de Vere White, Ralph, & Loots, Gabriela G. Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice. United States. https://doi.org/10.3390/ijms20204983
Martin, Kelly A., Hum, Nicholas R., Sebastian, Aimy, He, Wei, Siddiqui, Salma, Ghosh, Paramita M., Pan, Chong-xian, de Vere White, Ralph, and Loots, Gabriela G. Wed .
"Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice". United States. https://doi.org/10.3390/ijms20204983. https://www.osti.gov/servlets/purl/1867541.
@article{osti_1867541,
title = {Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice},
author = {Martin, Kelly A. and Hum, Nicholas R. and Sebastian, Aimy and He, Wei and Siddiqui, Salma and Ghosh, Paramita M. and Pan, Chong-xian and de Vere White, Ralph and Loots, Gabriela G.},
abstractNote = {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.},
doi = {10.3390/ijms20204983},
journal = {International Journal of Molecular Sciences (Online)},
number = 20,
volume = 20,
place = {United States},
year = {Wed Oct 09 00:00:00 EDT 2019},
month = {Wed Oct 09 00:00:00 EDT 2019}
}
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