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"Genome Protector" also controls cell development

Back - developed: cancerous tissue in the muscle (right), here by a Rhabdomyosarkompatienten, is very different from normal muscle tissue: the muscle cells look like at the beginning of their development, poorly developed and less specialized. So they can no longer fulfill their tasks. © Cancer Cell / Cam et al. Oct 2006
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Also known as the "guardian of the genome", p53 not only regulates cell division and cell death in diseased cells: the "tumor suppressor" also monitors the development and specialization of the healthy cell - making it the best prevention of cancer. This p53 gets support from his family members, p63 and p73. This is what scientists report in the latest issue of "Cancer Cell".

P53 made headlines as the "guardian of the genome". His role in errors in the genetic material, the healthy cells to cancer cells can: stop further division of the cells or bring about immediate cell death. Thus, p53 prevents the formation of tumors. Its function in the healthy cell, however, was previously unknown. This is different for two members of the p53 protein family: p63 and p73. These have been known for some years to be responsible for the normal development of, for example, neurons, immune cells or muscle cells, but also to control the cell for cell death.

The researchers led by Hakan Cam and Thorsten Stiewe from the Rudolf Virchow Center and the Department of Dermatology and Pathology at the University of Würzburg examined muscle cells during their development and found that not only p63 and p73 play a crucial role in muscle development, but also p53.

If these three proteins are missing or disrupted in a muscle cell, the cell stops its entire development program and the risk of becoming a cancer cell increases. This is exactly what happens in cells of rhabdomyosarcoma, a soft tissue tumor that forms primarily in children during muscle development. The entire p53 family regulates both: development and cell death.

p53 family with hybridization

But what is the reason for this hybridization of the p53 family? The higher a cell develops, the more specialized it becomes. It is already known that highly specialized cells rarely develop into a cancer cell. The cell development and cell specialization called cell differentiation seems to be a direct cancer protection. Thus, the control of differentiation processes in addition to the cell cycle inhibition and cell death is another mechanism of the p53 family against tumor formation. display

Another result caused a great surprise among the researchers: Under the p53 family hides a black sheep. A truncated form of the p73 protein, called DeltaNp73. This blocks all three family members and turns the cell into a cancer cell in no time. It is therefore no wonder that in other tumors, such as breast tumors, neuroblastomas and melanomas DeltaNp73 concentration is greatly increased.

The Würzburg researchers now want to find out whether the p53 family fulfills the same functions in other cancers. What did the researchers learn for a possible cancer prevention or therapy? "The DeltaNp73 and p53 proteins are potential targets for drugs in cancer therapy, and if DeltaNp73 can be blocked and p53 is activated, cells could regain their normal development and specialization - and that protects them against cancer ", says Stiewe. But it will still be a long way to go.

(idw - Rudolf Virchow Center / DFG - Research Center for Experimental Biomedicine, 18.10.2006 - DLO)