In more than half of all prostate tumors two genes - one for the transcription factor, called the ERG, the other - a gene induced testosterone called TMPRSS2 - merge together, which leads to overexpression of ERG. TMPRSS2-ERG protein makes prostate cells cancerous, but exactly how it's done, and what can be done to avoid this, scientists are not clear.
In an article published in Molecular Cell, the research team led by Gabriel Sandoval, John Pooleys, wide profile of the Institute member William Hahn and the Institute and co-director of the program a member of Epigenomics Cigall Kadoch showed that the fusion protein is involved in the act of molecular piracy, dialing cellular machine called complex the BAF, to help her load the gene expression program that otherwise would have been silent in the normal cells of the prostate gland. This is how they discovered contributes to the transformation of prostate cells into cancerous cells and may provide a new opportunity for the development of prostate cancer.
Transcription factors such as ERG, perform a variety of tasks that help the cell to express the right genes at the right time. The cells are usually quite picky about which transcription factors they use to express certain only at certain times in the course of their development and growth. Normal prostate cells, for example, do not produce and do not use the ERG, but the gene fusion TMPRSS2-ERG pushes them to it.
To understand the consequences of this activity, the team joined several employees, including the participants of the Broad's Cancer Program and Proteomics Platform program, to find out which proteins are partners with faziruemym ERG factor in cancer cells of the prostate gland.
The result was several members of BAF - complex proteins that work together to open the tightly packed DNA for transcription. Using a mixture of cell lines and organoid model of prostate cancer, the team found that a protein overexpressed TMPRSS2-ERG BAF steerable systems, causing them to open the field of the DNA of prostate cells, otherwise they would not be included normally inactive genes and causing the cells to turn into cancer.
The Panel also noted that the ERG relies on BAF complexes to carry out their dirty work; in their experiments, suppression of BAF members ceased gene program activated TMPRSS2-ERG. A drug that interferes with the interaction of BAF and TMPRSS2-ERG, in their opinion, may alter gene expression of prostate cancer powerful therapeutic means.
This is not the first time BAF complex capture faced Kadoch laboratory. Previously they reported that another fusion protein, called SS18-SSX, similar command BAF complexes in a rare cancer called synovial sarcoma, and that the fusion protein EWS-FLI1 perenatselyaet BAF-complexes in other tumor calledEwing's sarcoma.