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Telomere failure, telomerase activation drive prostate cancer progression
Date:2/21/2012

HOUSTON - Genomic instability caused by an erosion of the protective caps on chromosomes, followed by activation of an enzyme that reinforces those caps, allows malignant cells to evade destruction and acquire more deadly characteristics, researchers report in an Online Now article at the journal Cell.

In a strain of mice engineered to develop prostate cancer, all mice that went through this two-step process developed lethal cancer and 25 percent had the disease spread to the spine. Two groups of mice that avoided this cycle developed only precancerous lesions or localized prostate cancer.

A comparative analysis of genetic changes in the metastatic mouse tumors and those found in metastatic human prostate cancer identified the Smad4 gene as a driver in bone metastasis. Fourteen other genes were found to be associated with human prostate cancer prognosis.

The research focused on telomeres - repeat nucleotide sequences at the tips of chromosomes that prevent genomic damage during cell division. Telomeres shorten with each cell division, eventually permitting genomic instability in the cells that normally causes these abnormal cells to die.

In cancer the enzyme telomerase becomes activated and lengthens telomeres, preserving damaged cells to survive and reproduce. Telomerase is inactive in normal cells.

Telomerase activation confers new strengths on tumors

"These in vivo mouse studies, together with human and mouse prostate cancer genomic data, provide evidence that telomere dysfunction plays a critical role in prostate cancer initiation and progression," said co-senior author Lynda Chin, M.D., professor and chair of The University of Texas MD Anderson Cancer Center's Department of Genomic Medicine.

"Our studies also show that telomerase activation after genomic instability caused by telomere dysfunction enables evolving cancers to progress and acquire new biological properties, includ
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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