The MYC Oncogene Initiates and Maintains Metastasis in Mouse Prostate Cancer Model

A mouse metastatic prostate cancer model is expected to enable researchers to better investigate the causes of the disease while at the same time test new therapeutics to treat it.

The RapidCaP genetically engineered mouse (GEM) system was developed by investigators at Cold Spring Harbor Laboratory (NY, USA) who injected viral genes directly into mouse prostate tumors in order to induce them to metastasize.

Examination of these animals and analysis at the molecular level revealed that PI 3-kinase activity, a well-known modulator of prostate cancer, was absent from the RapidCaP metastasized tumors, and that the MYC oncogene was acting as the driving force behind the spread of the tumor. Indeed, they found that prostate tumors could be driven to metastasize simply by increasing the amount of Myc protein.

MYC (v-myc myelocytomatosis viral oncogene homolog protein) is a transcription factor that activates expression of a great number of genes through binding on consensus sequences and recruiting histone acetyltransferases (HATs). By acting as a transcriptional repressor in normal cells, MYC has a direct role in the control of DNA replication. The MYC protein (c-Myc) is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis, and cellular transformation. It functions as a transcription factor that regulates transcription of specific target genes. Mutations, overexpression, rearrangement, and translocation of this gene have been associated with a variety of hematopoietic tumors, leukemias, and lymphomas, including Burkitt lymphoma.

The investigators used RapidCaP to show that Myc both triggered local prostate metastasis and was critical for its maintenance. They further reported in the January 20, 2014, online edition of the journal Cancer Discovery that by treating these animals with the drug JQ1, which reduces the amount of Myc in cells, they could shrink the metastases, suggesting that the switch to Myc was required for maintenance of tumor cells that have metastasized throughout the body.

“The RapidCaP system has revealed a specific role for Myc as a druggable driver of metastasis in prostate cancer,” said senior author Dr. Lloyd Trotman. “So there is hope that our model provides a fast and faithful test-bed for developing new approaches to cure the type of prostate cancer that today is incurable.”

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Cold Spring Harbor Laboratory