Researchers found a byproduct of cholesterol that resembles estrogen fuels breast cancer growth.
The team found statins (anti-cholesterol drugs) may diminish the harmful effects of the molecule, a Duke University Medical Center news release reported.
"A lot of studies have shown a connection between obesity and breast cancer, and specifically that elevated cholesterol is associated with breast cancer risk, but no mechanism has been identified," senior author Donald McDonnell, Ph.D., chair of the Department of Pharmacology and Cancer Biology at Duke, said. "What we have now found is a molecule - not cholesterol itself, but an abundant metabolite of cholesterol - called 27HC that mimics the hormone estrogen and can independently drive the growth of breast cancer."
Estrogen has been shown to feed about 75 percent of all breast cancers. The researchers observed 27-hydroxycholesterol (27HC) behaved similarly to estrogen in animal test subjects.
The team worked to determine if this estrogen activity could promote breast cancer growth on its own, and if using drugs to control it elicited an improvement.
The researchers monitored the direct involvement of 27HC in breast cancer in mice, and found that when they were treated with antiestrogens the 27HC was stopped.
"The worse the tumors, the more they have of the enzyme," lead author Erik Nelson, Ph.D., a post-doctoral associate at Duke, said. Nelson said
"Gene expression studies revealed a potential association between 27HC exposure and the development of resistance to the antiestrogen tamoxifen. Their data also highlights how increased 27HC may reduce the effectiveness of aromatase inhibitors, which are among the most commonly used breast cancer therapeutics," Nelson said, according to the news release.
"This is a very significant finding," McDonnell said. "Human breast tumors, because they express this enzyme to make 27HC, are making an estrogen-like molecule that can promote the growth of the tumor. In essence, the tumors have developed a mechanism to use a different source of fuel."
