5 January 2015

Gene keeps potential cancer cells in check

Cancer Research

To prevent cancer development, it is crucial that cells with damaged DNA do not divide. Researchers from BRIC, University of Copenhagen, have just established a mechanism that blocks cell division in damaged cells. If a cell’s DNA is damaged by irradiation, the gene Cyclin-F halt cell division. The results are important to understand how to constrain cancer and are published in Nature Communications.

A crucial finding in cancer research was made back in 1979 with the discovery of the gene p53. p53 turned out to be part of a fine-tuned machinery that monitors cell division through a number of checkpoints. Here cells go through an inspection, and p53 stops any growth of potential damaged cells at the G2 checkpoint. But surprisingly, p53 does not work until 24-48 hours after DNA damage occurs. What actually prevents damaged cells from dividing in the meantime has been uncertain.

-How our cells have been able to maintain a checkpoint before p53 becomes active have been unclear. What our new results show is that another gene called Cyclin-F plays a key role in the early phase after DNA damage, says associate professor Claus Storgaard Sørensen, who heads the research group at BRIC.

Oncogene is kept in check by Cyclin-F

The researchers screened 559 genes trying to find new genes that might be involved in regulating the cell division process. First they irradiated human cells in order to damage the cell DNA. Then they examined whether any of the 559 genes would affect the division process. Here it immediately became obvious that the gene Cyclin-F was necessary in order to maintain the checkpoint system as well as to block the division of cells damaged by radiation. Researchers had to further study the function of Cyclin-F in order to understand the significance of the gene.    

DNA damage- Our investigations revealed that Cyclin-F acts by inhibiting the function of the so-called oncogene B-Myb, a gene that normally stimulates cell division. Cyclin-F keeps B-Myb in check and in this way prevents cell division among damaged cells, explains Ditte Klein and Saskia Hoffmann, who conducted the experiments as part of their PhD and master studies.

The oncogene B-Myb is a well-known gene present in several types of cancer, including breast, prostate, ovarian and liver cancer. Here the high gene activity contributes to cancer cell division. Just now, the researchers are studying whether Cyclin-F levels are changed in the different types of cancer, as this may affect B-myb’s ability to stimulate the growth of cancer.

-It is crucial to understand those mechanisms that normally protect our cells against uncontrolled cell division, if we want to understand cancer. If we manage to understand these mechanisms, then we might be able to control the mechanisms chemically in cancer cells and offer new cancer treatments, says Claus Storgaard Sørensen.

cell cycleFACTS

The process of cell division is normally carefully regulated. When cancer occurs, it is often because of mutations in genes that regulate this process. While some genes stimulate normal cell division, others inhibit cell division. There is often an increased activity of such stimulating genes in cancer, also called oncogenes (cancer genes). A change in genes that inhibit cell division in different types of cancer is also present. These are called tumor suppressor genes, since they prevent cell division in cancer cells and hence growth.