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Preventing cancer: Scientists identify a useful piece of JNK

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06.03.2003

The JNK signaling pathway allows cells to respond to changes in their extracellular environment and in doing so, controls many aspects of cell function including cell proliferation, differentiation and death. Studies have also shown that this pathway plays a role in cancer, although it has been unclear whether active JNK signaling can accelerate or protect cells from becoming cancerous. Several studies using cultured cells have suggested that JNK signaling may be important for promoting tumor cell development, while studies of tumors from human patients have indicated that JNK signaling may act to suppress tumor development.

Dr. Davis and colleagues set out to address the role of JNK signaling in tumor formation using cells from mice that have been engineered to be deficient in JNK signaling. They demonstrated that in vitro, JNK signaling does indeed play a role in transforming normal cells into those displaying the characteristics of tumor cells.

However, when they moved their experiments into a mouse model of tumor development, it was clear that JNK signaling is not required for tumor formation. In fact, the scientists actually found the opposite - that the absence of JNK signaling resulted in a dramatic increase in the number and growth of tumors when compared to control animals. This result suggests that in vivo, JNK signaling acts to suppress tumor development.

The scientists went on to examine how JNK signaling puts the brakes on tumor development and protects from disease. "The mechanism of action of JNK in tumor suppression involves the induced suicide of the defective cells that are destined to become tumor cells," explains Dr Davis. Cell suicide (or apoptosis) of unhealthy cells is a key protective mechanism against the development of cancer. In the mice studied in these experiments, loss of JNK signaling prevented apoptosis of unhealthy cells and thus promoted tumor cell survival.

Dr. Davis also comments on the implications of these findings: "Our study indicates that mutations in the JNK signaling pathway genes in human tumors may contribute to malignant cancer progression. It is likely that this information will be useful for diagnosis and for the design of appropriate treatment strategies." He points out that attempts to target anti-cancer drugs to inhibit the JNK pathway should be treated with caution, as in some cases this is likely to do more harm than good. Finally, he offers a word of caution: "Our conclusions are limited to the analysis of mice with a single type of cancer.

Further studies are required to extend our conclusions to humans and to the study of other types of cancer." Nevertheless, the work offers new insights into the cellular changes underlying some cancers and underscores the need for in vivo experiments to better understand the role of specific signaling.

Michele McDonough | Source: EurekAlert!
Further information: www.cshl.org/

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