Newly found enzymes may play early role in cancer

Dec 24, 2008

Researchers have discovered two enzymes that, when combined, could be involved in the earliest stages of cancer. Manipulating these enzymes genetically might lead to targeted therapies aimed at slowing or preventing the onset of tumors.

"We could conceivably reactivate a completely normal gene in a tumor cell - a gene that could prevent the growth of a tumor if reactivated," says David Jones, Ph.D., professor of oncological sciences at the University of Utah and senior director of early translational research at the university's Huntsman Cancer Institute (HCI).

"We believe this could be one of the earliest processes to go wrong in cancer," he adds. "By manipulating these enzymes, we could possibly prevent or slow the onset of tumors."

The enzymes appear to control an "on-and-off switch" for critical genes that could trigger cancer or numerous other diseases and birth defects. The research is published in the December 26 issue of Cell.

Using zebrafish that share similar genetics to humans, the HCI scientists identified a previously unknown enzyme process that controls the levels of DNA methylation on genes.

"Methylation is a cellular process that is required for healthy cell growth and development, but it can go awry in cancer and diseased cells," says Brad Cairns, Ph.D., HCI investigator and professor of oncological sciences at the University of Utah. "You can think of DNA methylation as an on-and-off switch. Methylation silences or 'shuts off' genes that need to be turned off or are not functioning as they should, whereas the reverse process called demethylation 'turns on' healthy genes and genes needed at critical times in development," he says.

In cancer, this methylation process goes haywire, leading to tumor growth. Genes that should be "turned on" are not and vice versa.

The significance of this research is the discovery of two enzymes involved in DNA demethylation. Defects in DNA methylation balance are strongly associated with the early development of cancer, other diseases and birth defects, and the scientists say their study is the first clear evidence that this enzyme system plays a critical role in maintaining this balance. They also believe it's a process that can be reversed.

Further research will reveal if DNA methylation levels can be manipulated genetically. If so, it could lead to drugs to reactivate particular genes and suppress tumor growth. Remarkably, this system also helps protect the genome from mutations.

"We discovered a pair of enzymes that can remove methylated DNA, but if these enzymes work improperly, they will instead enhance the rate of mutations in methylated DNA and cause cancer progression," says Jones. "The question now is, when they work improperly, can we find ways to shut them off and prevent these mutations?"

The enzymes leading to DNA demethylation involve the coupling of a 5-meC deaminase enzyme, a G:T glycosylase enzyme and Gadd45, which is not an enzyme.

Source: University of Utah

Explore further: Can orange juice, grapefruit raise your melanoma risk?

Related Stories

Protein scaffold

May 27, 2015

Right before a cell starts to divide to give birth to a daughter cell, its biochemical machinery unwinds the chromosomes and copies the millions of protein sequences comprising the cell's DNA, which is packaged ...

Researchers find 'decoder ring' powers in micro RNA

May 26, 2015

MicroRNA can serve as a "decoder ring" for understanding complex biological processes, a team of New York University chemists has found. Their study, which appears in Proceedings of the National Academy of Sciences, points ...

Recommended for you

Researchers confirm gene p73's role in tumor growth

17 hours ago

A team of researchers at National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH) has determined dual functionality gene p73, in both the promotion and suppression in tumour growth. The NCCS team also ...

User comments : 0

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.