Re: [MOL] Cancer News Stories 10/28/98/Tamoxifen [02437] Medicine On Line


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Re: [MOL] Cancer News Stories 10/28/98/Tamoxifen



WESTPORT, Oct 27 (Reuters Health) - Diethylstilbestrol (DES) causes
reproductive tract abnormalities in prenatally exposed female mice because
it deregulates the Wnt7a gene during the postnatal period when uterine
morphogenesis occurs, a New York research team reports. 

According to the researchers, the findings have implications for the study
of tamoxifen and other DES-like drugs. 

In previous research, Dr. David A. Sassoon and a colleague, of Mount Sinai
Medical Center in New York, found that female mice lacking Wnt7a have
reproductive tract malformations similar to those observed in female mice
exposed to DES prenatally. 

To confirm the hypothesis that loss of Wnt7a accounts for the mouse DES
syndrome, Dr. Sassoon and associates treated pregnant mice with DES
suspended in sesame oil or with oil alone. Among female offspring of the
control mice, the team detected normal uterine levels of Wnt7a on the day
of birth, according to their report in the November issue of Nature
Genetics. 

In contrast, female offspring of DES-exposed mice had low uterine
expression of Wnt7a on the day of birth, the investigators found. Wnt7a
levels returned to normal 5 days after birth and did not decline
subsequently. 

Dr. Sassoon's group concludes that "...DES exposure results in
downregulation of Wnt7a during a critical postnatal period, thereby
interfering with proper uterine morphogenesis." 

Noting that tamoxifen doubles the incidence of uterine cancer, according to
one report, the authors add that "[u]nderstanding the molecular responses
to breast and uterine tissues to steroidal pharmacological agents will be
of high importance should their use increase." 

"I don't want to ring an alarm bell about tamoxifen per se," Dr. Sassoon
told Reuters Health. "It's just that there was never an explanation as to
how DES actually created a precancerous condition. We thought by being able
to furnish an explanation, any other estrogenic-like molecules that are
being used could be looked at now with more understanding as to what is
going on." 

"I'm hoping this will crack open the problem," Dr. Sassoon added. 

Nat Genet 1998;20:228-230. 

Copyright 1998 Reuters Limited. All rights reserved. Republication or
redistribution of Reuters content is expressly prohibited without the prior
written consent of Reuters. Reuters shall not be liable for any errors or
delays in the content, or for any actions taken in reliance thereon. 

----------
> From: Robert W. Neill, Jr. <rwneill@rwneill.com>
> To: Recipient list suppressed
> Subject: [MOL] Cancer News Stories 10/28/98
> Date: Wednesday, October 28, 1998 4:51 PM
> 
> CancerDaily
> October 28, 1998
> http://rwneill.com
> 
> Molecular assay allows improved staging of melanoma
> http://ipn.intelihealth.com/ipn/ihtIPN?c=200311
> _
> Findings about DES damage in mice have 
> implications for tamoxifen research
> http://ipn.intelihealth.com/ipn/ihtIPN?c=200244
> 
> -----
> Robert W. Neill, Jr.
> CancerDaily Publisher
> http://www.rwneill.com
> 
> To subscribe to CancerDaily, send a blank email to
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> 
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