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Estrogen may reprogram prostate cancer gene in black men
Lack of chemical tags may lead to higher risk
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WASHINGTON — A new study shows how chemical tags on DNA may lead to higher rates of prostate cancer in black men. And estrogen may play a role, researchers reported June 12 at a meeting of the Endocrine Society in Washington, D.C.

“It may be that estrogen can reprogram the genome,” says study coauthor Wan-yee Tang of the University of Cincinnati in Ohio.

In black men, Tang and her colleagues found fewer of the chemical tags, called methyl groups, near the portion of DNA that encodes a gene active in the prostate than the team found in white men. The lack of these epigenetic tags may alter the gene’s activity and upset the balance of other proteins in the cell, making the cell more vulnerable to becoming cancerous, the researchers propose.

Earlier studies have shown that black men face a higher risk of prostate cancer than white men. Black men also have higher average levels of estrogen than white men. And experiments on rats have shown that high doses of estrogen take away methyl groups near the prostate gene PDE4D4, leading to abnormally high levels of the PDE4D4 protein.

Tang and her colleagues compared methyl groups among black and white men on a part of the DNA that controls the activity of PDE4D4. Cancer cells from white men had fewer methyl groups near the PDE4D4 gene than noncancerous cells. In cells from black men, though, both the cancerous and noncancerous cells had fewer methyl groups in the region, meaning that the pattern of methyl groups even in noncancerous cells looked like that of cancerous cells from whites. These methyl groups may be stripped away by higher levels of estrogen in black men, Tang and her colleagues suggest.

PDE4D4 protein keeps another molecule, called cyclic AMP, in check. Abnormal levels of cyclic AMP may ultimately increase the risk of prostate cancer, Tang says.


Found in: Body & Brain and Genes & Cells
Comments 2
  • cAMP is not a protein, it is a nucleotide.
    Could the protein be adenylate cyclase?
    NMBioguy NMBioguy
    Jun. 16, 2009 at 12:49pm
  • In the field of molecular biology, the cAMP dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor triggered signaling cascade used in cell communication. It is NOT a nucleotide, but derived from ATP (Adenosine triphosphate)an important agent of intracellular energy transfer. The point here is that estrogen seems to play a role in cancer through methylation ( turning on or off) of various genes in the prostate. Estrogen de-methylation has also been implicated in other cancers of the breast and colon.
    James Boettcher James Boettcher
    Jun. 17, 2009 at 2:11am
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Citations & References:
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  • W.Y. Tang, M.P. Revelo, L. Levin, S.M. Ho. A New Signature for Prostate Cancer Risk Disparity: Differential Methylation of Phosphodiesterase IV Variant 4 between Black and White-Americans. Presented at a poster session: BENCH TO BEDSIDE: Hormonal Signaling in Prostate Cancer, The Endocrine Society meeting, Washington, D.C. June 12, 2009. Abstract P3-59, available at www.abstracts2view.com/endo
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