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Scientists Identify Genetic Link Between Cancer And Aging

Date:
June 24, 2003
Source:
Cold Spring Harbor Laboratory
Summary:
A collaboration of scientists mainly from the Fred Hutchinson Cancer Center and at the University of Washington (Seattle) has made an important discovery linking the powerful cancer-causing oncogene, myc, with the gene behind the premature aging disease, Werner syndrome.
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A collaboration of scientists mainly from the Fred Hutchinson Cancer Center and at the University of Washington (Seattle) has made an important discovery linking the powerful cancer-causing oncogene, myc, with the gene behind the premature aging disease, Werner syndrome. Their finding reveals that the MYC oncoprotein turns-on Werner syndrome gene expression, and posits the Werner syndrome gene as a potentially important participant in MYC-induced tumorigenesis.

Werner syndrome is a rare genetic disorder characterized by the appearance of old age beginning after puberty. It is caused by mutations in the Werner syndrome gene (WRN), which resides on the short arm of human chromosome 8. The WRN gene encodes a DNA helicase (an enzyme that unwinds DNA) involved in DNA replication and repair.

As published in the July 1 issue of Genes & Development, Dr. Carla Grandori and colleagues have discovered that WRN expression is regulated by the MYC oncoprotein, which is implicated in about one third of all human cancers.

As Dr. Grandori explains, "We uncovered a role in oncogenesis for a gene, WRN, whose function was known to be important in maintaining youth of the whole organism. This study was prompted by the characteristic ability of tumor cells in culture to multiply indefinitely and thus to exhibit permanent youth. Our results are consistent with the hypothesis that genetic programs that limit organismal aging may, at the cellular level, promote tumor development, thus constituting a double sword. On the positive side, we hope that our study will provide a new therapeutic target able to trigger tumor cells into senescence."

Dr. Grandori and colleagues found that MYC binds directly to the WRN gene promoter to activate WRN expression in vitro and in vivo. The authors demonstrated that in both WRN-deficient and WRN-depleted human cells, MYC over-expression drives the cells into a state of permanent growth arrest, called cellular senescence. This finding suggests that WRN normally functions to prevent cellular senescence and thereby promote cell proliferation.

The implications of these findings for tumor development is that up-regulation of WRN by oncogenic MYC expression could contribute to tumor formation by suppressing cellular senescence. In support of this hypothesis, the authors note that Werner syndrome patients, although predisposed to certain cancers, do not typically display MYC-associated tumor types (e.g. Burkitt or diffuse large B-cell lymphomas, breast and prostate carcinomas).

While further work is needed to delineate the precise role of WRN in tumorigenesis, this report brings to light a heretofore unrecognized therapeutic approach: That the inhibition of WRN in MYC-induced tumor cells could induce cellular senescence and impede cancer progression.

In commenting on the work one of the participating investigators, Dr. Ray Monnat of the University of Washington notes that "We have recognized deep links between cell senescence and tumorigenesis for some time. It's gratifying to see another of these links identified that is conceptually interesting and may have practical importance."


Story Source:

The above post is reprinted from materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


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Cold Spring Harbor Laboratory. "Scientists Identify Genetic Link Between Cancer And Aging." ScienceDaily. ScienceDaily, 24 June 2003. <www.sciencedaily.com/releases/2003/06/030624085707.htm>.
Cold Spring Harbor Laboratory. (2003, June 24). Scientists Identify Genetic Link Between Cancer And Aging. ScienceDaily. Retrieved July 1, 2015 from www.sciencedaily.com/releases/2003/06/030624085707.htm
Cold Spring Harbor Laboratory. "Scientists Identify Genetic Link Between Cancer And Aging." ScienceDaily. www.sciencedaily.com/releases/2003/06/030624085707.htm (accessed July 1, 2015).

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