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UCLA cancer researchers discover new signaling pathway that controls cell development and cancer
Date:9/23/2010

turning off the 136 genes identified in the study. Defects in the newly discovered cell signaling pathway don't allow cells to progress to their natural end point by blocking normal gene silencing. The less mature cells become stuck where they are, dividing too rapidly and potentially resulting in lymphoma or leukemia.

Usually DNA damage is thought to be associated with environmental factors, such as exposure to too much sun or to toxic chemicals. Chemotherapy also damages cell DNA. However, Teitell and his team discovered that a normal process, the creation of antibodies to battle infection, results in physiologic DNA damage that also activates the identified signaling pathway.

Teitell, in previous studies, discovered that the gene TCL1 can cause B-cell cancers, including various types of lymphomas, if it is not turned off at the right time in development. Activation of this new signaling pathway, in fact, is the mechanism that shuts the TCL1 oncogene down at the appropriate time. If a pathway defect develops, TCL1 and the other 135 genes remain elevated and cancer may arise.

B-cells are lymphocytes that play a large role in immune responses and they make antibodies in response to infection or vaccination. They divide at the highest rate in the human body, faster than skin, hair or cells of the gastrointestinal tract. In making antibodies to fight infection or in response to a vaccine, these rapidly proliferating cells undergo DNA damage in order to make better, more effective antibodies. The body, in effect, is trading off the potential harm caused by added DNA damage in order to effectively ward off a more immediate invader.

The rapid cell cycling process that occurs during antibody assembly and testing by the immune system needs to be halted at the right time, Teitell said. The body naturally turns off that process after about two to three weeks. A defect in the new pathway interrupts that natural stop signal and blo
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Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California -- Los Angeles
Source:Eurekalert

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