Reduction of Oncogene Activity Causes Cancer Cells to Revert to Normal

Cancer researchers working with a mouse model have found that by reducing the activity of the Myc oncogene, they could reverse the uncontrolled growth of cancer cells and return them to a normal, healthy state.

All normal cells require Myc activity. However, Myc overexpression causes cells to grow too large and multiply uncontrollably. Previous studies have shown that eliminating Myc caused the death of tumor cells but had the same effect on normal tissues.

In the current study investigators at Stanford University (Palo Alto, CA, USA) worked with mice that had been genetically engineered to develop Myc-driven tumors in response to a chemical in their drinking water. After triggering tumor development at high levels of Myc activity, they gradually reduced the level of Myc. During this process they monitored both the genomic - oligonucleotide microarray analysis and quantitative PCR were used to identify changes in expression in 3,921 genes – and proteomic status of the cells. In the latter case, two-dimensional protein analysis followed by mass spectrometry, phospho-flow fluorescence-activated cell sorting, and antibody arrays were employed.

Results published in the July 1, 2008, issue of the journal Cancer Research revealed that as the Myc concentration reached the critical level where cancer cells began to revert to normal 2,348 genes were down-regulated while 1,573 were up-regulated, and proteins involved in mRNA translation decreased. In short, at the MYC threshold level, there was a loss of the oncogene's ability to maintain tumorigenesis, with associated shifts in gene and protein expression that reestablished cell cycle checkpoints, halted protein translation, and promoted apoptosis.

"In the past, scientists have shown that cancer signals such as Myc are like light switches,” said senior author Dr. Dean Felsher, associate professor of oncology and pathology at Stanford University. "Now we know that, in some cases, you do not need to turn the light completely off. We were able to experimentally prove that we can turn Myc off a little bit, or for a little time, and that is enough to have a profound effect on cancer.”


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