Breast cancer tumor suppressor gene silenced by low O2

August 16, 2011, American Society for Microbiology

Low oxygen can silence the BRCA1 tumor suppressor gene and contribute to the progression of cancer, according to a paper in the August 2011 issue of the journal Molecular and Cellular Biology. Silencing this particular gene is one of the steps on the malignant pathway to breast cancer. The research may ultimately lead to ways of reactivating this and other tumor suppressor genes, in order to thwart cancer, says corresponding author Peter Glazer of Yale University, New Haven.

This study grew out of Glazer’s laboratory’s previous findings that low stress to cells can cause changes in expression of many human , sometimes boosting, and sometimes reducing expression. “We had found a few years ago that hypoxia reduces expression of BRCA1, and so I had the idea to ask whether it could drive silencing of the gene,” says Glazer. 

Hypoxia is common in human tumors, partly because newly emerging tumors lack blood vessels. “They become hypoxic because they don’t get enough blood,” says Glazer. As they enlarge, they begin to grow blood vessels, in a process known as angiogenesis. But “that process is never perfect, so tumors have a very variable and incomplete blood supply,” says Glazer. “That makes them more genetically unstable, and helps drive them towards more malignant properties,” he adds, citing earlier work by his laboratory.

The silencing could be a first step towards cancer, but Glazer thinks it more likely is a later step, since without the tumor, the hypoxia that drives gene silencing is less likely to occur, says Glazer.  

Understanding the mechanism of reduced expression would open the way to research that could lead to strategies for interfering with the gene silencing. What we know so far: the mechanism for the silencing involves the histones, proteins that wrap around the chromosomes when they are silent, but which unwrap around genes that are being expressed. Glazer showed that the silencing of BRCA1 is accompanied by a change in the histones, called methylation, which is frequently seen when gene expression is reduced.

“We then found that one particular enzyme, called lysine demethylase [LSD1] is manipulating the methylations,” says Glazer. Finding a way to block that enzyme could lead to reactivating BRCA1, he says, noting that this might be done by finding a small molecule that inhibits that enzyme’s activity. Such a drug might reactivate other tumor suppressors as well, he says. 

Glazer thinks that cell stress in general caused by hormones or environmental toxins may lead to silencing BRCA1, and he plans to investigate that hypothesis.

Explore further: Silence of the genes

More information: Y. Lu, et al., 2011. Hypoxia-induced epigenetic regulation and silencing of the BRCA1 promotor. Mol. Cell. Biol. 31:3339-3350

Related Stories

Silence of the genes

July 22, 2011
A molecular mechanism by which gene silencing is regulated at the genome-wide level in plants has been uncovered by a research team led by Motoaki Seki of the RIKEN Plant Science Center, Yokohama, Japan. The researchers ...

Penn study on silencing of tumor suppressor gene suggests new target for lymphoma

August 10, 2011
Mariusz A. Wasik, MD, professor of Pathology and Laboratory Medicine, and Qian Zhang, MD, PhD, research assistant professor, both from the Perelman School of Medicine at the University of Pennsylvania, and their colleagues, ...

Researchers reveal PAX gene’s role in cancer

May 24, 2011
(Medical Xpress) -- University of Otago researchers have uncovered further evidence that PAX genes − members of a small family of genes that play important roles in embryonic development – also allow cancer cells ...

Recommended for you

Study tracks evolutionary transition to destructive cancer

February 23, 2018
Evolution describes how all living forms cope with challenges in their environment, as they struggle to persevere against formidable odds. Mutation and selective pressure—cornerstones of Darwin's theory—are the means ...

Researchers use a molecular Trojan horse to deliver chemotherapeutic drug to cancer cells

February 23, 2018
A research team at the University of California, Riverside has discovered a way for chemotherapy drug paclitaxel to target migrating, or circulating, cancer cells, which are responsible for the development of tumor metastases.

Lab-grown 'mini tumours' could personalise cancer treatment

February 23, 2018
Testing cancer drugs on miniature replicas of a patient's tumour could help doctors tailor treatment, according to new research.

An under-the-radar immune cell shows potential in fight against cancer

February 23, 2018
One of the rarest of immune cells, unknown to scientists a decade ago, might prove to be a potent weapon in stopping cancer from spreading in the body, according to new research from the University of British Columbia.

Putting black skin cancer to sleep—for good

February 22, 2018
An international research team has succeeded in stopping the growth of malignant melanoma by reactivating a protective mechanism that prevents tumor cells from dividing. The team used chemical agents to block the enzymes ...

Cancer risk associated with key epigenetic changes occurring through normal aging process

February 22, 2018
Some scientists have hypothesized that tumor-promoting changes in cells during cancer development—particularly an epigenetic change involving DNA methylation—arise from rogue cells escaping a natural cell deterioration ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.