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Protein disables p53, drives breast cells toward cancer transition
Date:12/15/2010

that these structural domains suggest that TRIM24 not only can read the histone code but is actually reading a very unusual alphabet spelling of the histone barcode. This unusual histone signature appears at estrogen-response elements-places in the DNA where estrogen receptors bind - and it is regulating estrogen-regulated genes that become overstimulated by TRIM24. These genes push cells into proliferation and probably into tumorigenesis.

Overexpressed TRIM24 cuts survival

When the researchers examined a number of breast cancer cell lines, they found that TRIM24 was overexpressed in each one. "Because TRIM24 is basically undetectable in normal cells," Barton said, "we believe that by virtue of its being overexpressed, it's negatively regulating p53 and overstimulating estrogen receptors that, in turn, promote the proliferation."

Collaboration with MD Anderson's Mien-Chie Hung, Ph.D., chair of the Department of Molecular and Cellular Oncology, further strengthened the case for TRIM24's role in breast cell proliferation and tumorigenesis. When pathologist Weiya Xia, M.D., screened biopsies of 128 breast cancer patients, she found that TRIM24 was overexpressed in 70 percent. These patients had a median overall survival rate of 50 months, meaning half of them survived at least to that point.

In 30 percent of the women, TRIM24 was either undetectable or expressed at very low levels. In these two groups, the women's breast cancer was non-metastatic, and 90 percent survived to 50 months.

Avenues of future research

"We propose that TRIM24 would be a great therapeutic target - the reason being that if you were to eliminate or inactivate TRIM24, you could potentially restart p53 function and decrease estrogen receptor function in breast tumor cells," Barton said. "In the case of ER-negative tumors, you might still have a chance to go for the p53, and in the case of breast cancers that are p53-negative you might stil
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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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