Author Interviews, Cancer Research / 30.11.2014
Discovery Pinpoints How Some Aggressive Cancers Turn Off Tumor Suppressor Genes
MedicalResearch.com Interview with:
Charles Brenner, PhD
Roy J. Carver Chair & Head of Biochemistry
Departments of Biochemistry & Internal Medicine
Carver College of Medicine
University of Iowa Iowa City, IA 52242
Medical Research: What is the background for this study? What are the main findings?
Dr. Brenner: KRAS mutations are extremely common in human malignancies. The KRAS gene is an oncogene that drives cell growth pathways and that leads to silencing and inactivation of tumor suppressor genes. It was known that KRAS mutant cancer cells silence tumor suppressor genes but the precise mechanism for gene silencing was not known. In this study, we discovered that KRAS mutations turn off the TET1 gene. TET1 functions as an "eraser" of gene silencing marks. When KRAS mutations occur, the TET1 eraser isn't expressed any longer, and a series of tumor suppressor genes become silenced. This is an essential part of the aggressiveness of KRAS-dependent cancers and is controlled by the ERK pathway that is turned on by KRAS. In short, KRAS turns on ERK, which turns off TET1. When TET1 is off, a set of tumor suppressor genes are also turned off, which drives cancer formation.
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