Developmental Reprogramming May Cause Cancer

Anderson Cancer Center (Houston, USA). Their study was published in the May 30, 2005, online Proceedings of the [U.S.] National Academy of Sciences.

The study was conducted with rats susceptible to benign uterine tumors, and the estrogen compound used was diethylstilbestrol (DES), a banned anti-miscarriage drug. However, the researchers believe their conclusions also have relevance for humans who inherit defective tumor-suppressor genes that make them susceptible to a number of different cancers. They could explain, for example, why some women who inherit BRCA1/2 gene defects develop breast cancer as adults while others with the same genes do not.

"The kind of developmental reprogramming we see from this work could represent an important determinate of risk in people genetically susceptible to hormone-dependent tumors, such as uterine, breast, and prostate cancer,” observed principal investigator Cheryl Walker, Ph.D., a professor in the department of carcinogenesis at M.D. Anderson. "It suggests that for gene-environmental interactions, the timing of the exposure may be critical, and it may happen much earlier than anyone ever suspected.”

The researchers designed a study using female rats genetically predisposed to develop uterine leiomyoma and exposed them to DES. For the experimental group, researchers used another set of genetically susceptible rats and exposed them to DES, which is highly estrogenic. By the time the rats reached adulthood (16 months), all of the rats in the experimental group had developed leiomyoma. In contrast, none of the DES-exposed rats that lacked the genetic defect developed tumors.

"The DNA of DES-exposed animals had been modified by DES in a way that changed how genes responded to estrogen, causing this tissue to be hypersensitive to the effects of this hormone,” noted Dr. Walker.




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