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Full-Text Articles in Medicine and Health Sciences
Multi-Focal Control Of Mitochondrial Gene Expression By Oncogenic Myc Provides Potential Therapeutic Targets In Cancer., Amanda R. Oran, Clare M. Adams, Xiao-Yong Zhang, Victoria J. Gennaro, Harla K. Pfeiffer, Hestia S. Mellert, Hans E. Seidel, Kirsten Mascioli, Jordan Kaplan, Mahmoud R. Gaballa, Chen Shen, Isidore Rigoutsos, Michael P. King, Justin L Cotney, Jamie J. Arnold, Suresh D. Sharma, Ubaldo E. Martinez-Outshoorn, Christopher R. Vakoc, Lewis A. Chodosh, James E. Thompson, James E. Bradner, Craig E. Cameron, Gerald S. Shadel, Christine M. Eischen, Steven B. Mcmahon
Multi-Focal Control Of Mitochondrial Gene Expression By Oncogenic Myc Provides Potential Therapeutic Targets In Cancer., Amanda R. Oran, Clare M. Adams, Xiao-Yong Zhang, Victoria J. Gennaro, Harla K. Pfeiffer, Hestia S. Mellert, Hans E. Seidel, Kirsten Mascioli, Jordan Kaplan, Mahmoud R. Gaballa, Chen Shen, Isidore Rigoutsos, Michael P. King, Justin L Cotney, Jamie J. Arnold, Suresh D. Sharma, Ubaldo E. Martinez-Outshoorn, Christopher R. Vakoc, Lewis A. Chodosh, James E. Thompson, James E. Bradner, Craig E. Cameron, Gerald S. Shadel, Christine M. Eischen, Steven B. Mcmahon
Department of Cancer Biology Faculty Papers
Despite ubiquitous activation in human cancer, essential downstream effector pathways of the MYC transcription factor have been difficult to define and target. Using a structure/function-based approach, we identified the mitochondrial RNA polymerase (POLRMT) locus as a critical downstream target of MYC. The multifunctional POLRMT enzyme controls mitochondrial gene expression, a process required both for mitochondrial function and mitochondrial biogenesis. We further demonstrate that inhibition of this newly defined MYC effector pathway causes robust and selective tumor cell apoptosis, via an acute, checkpoint-like mechanism linked to aberrant electron transport chain complex assembly and mitochondrial reactive oxygen species (ROS) production. Fortuitously, MYC-dependent …
Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman
Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman
Open Access Theses
Lung cancer is the leading cause of cancer deaths in the United States, accounting for 27% of all cancer induced deaths1. In an attempt to create a effective targeted therapy for the treatment of lung cancer, a strategy used to treat an activated KrasG12D/+;p53 R172H/+ transgenic lung cancer mouse model was to deliver a known tumor suppressive microRNA (miRNA) to stop tumor growth. The tumor suppressive miRNA let-7 was lentivirally delivered in the form of its primary transcript, pri-let-7a-1, and resulted in increased lung size and inflammation compared to lungs exposed to a control lentivirus. It was identified …