Athens, Ga. – Human cancer cells divide and conquer.
Unless physicians can control that division with surgery, chemotherapy or
radiation, the wildly dividing cells will eventually destroy a person’s life.
Researchers have known for some time that an enzyme called
telomerase is crucial to cancer’s progress. Now, for the first time,
researchers at the University of Georgia’s Franklin College of Arts and Sciences
have shown a mechanism that explains how two essential components of human
telomerase—normally active only in early prenatal development but turned back
on during cancer growth—are “recruited” from distinct sites in the cell to the
telomere, an area at the end of a chromosome that normally protects it from
destruction.
“Telomerase is reactivated in more than 90 percent of human
cancers,” said Michael Terns, professor of biochemistry and molecular biology
and genetics at UGA, “and the fact that telomerase keeps these telomeres
growing when it should be inactive is crucial for the proliferation of cancer.
That makes telomerase a very promising target for a potential drug to stop
cancers from spreading.”
The research was just published in the journal Molecular Biology of the Cell. Other
authors on the paper were Rebecca Terns, a senior research scientist also in
UGA’s department of biochemistry and molecular biology (Michael and Rebecca
Terns are a husband-wife team); Rebecca Tomlinson, a former doctoral student in
the Terns Lab; Eladio Abreu, a current graduate student in the Terns lab; Tania
Ziegler, also a former member of the Terns lab, now pursuing an M.D. degree;
Hinh Ly of Emory University; and Christopher Counter of Duke University Medical
Center. Rebecca and Michael Terns are also members of the University of Georgia
Cancer Center.
The two essential components of human telomerase are
telomerase RNA and telomerase reverse transcriptase. They are “recruited” to
telomeres during what is called the “S phase” (for synthesis) of the cell cycle
when DNA replication or synthesis occurs.
“What we have found is that during the remainder of the cell
cycle, telomerase RNA is found primarily in rather mysterious and, until
recently, little-understood structures called Cajal bodies,” said Rebecca
Terns. “Though science has known about Cajal [pronounced Ca-HAHL] bodies for more than a hundred years, what we have
discovered is that the localization of telomerase RNA to Cajal bodies and
telomeres is specific to cancer cells where telomerase is active.”
The new research shows for the first time that the
trafficking of telomerase RNA to both telomeres and Cajal bodies depends on the
presence of telomerase reverse transcriptase.
The Terns lab took advantage of the differences between
normal and cancer cells of many kinds to better understand the trafficking of
telomerase RNA.
“We examined a variety of factors that differ between normal
and cancer cells in order to identify factors that impact human telomerase localization,”
said Michael Terns. “Our results indicate that human reverse transcriptase is a
key determinant in human telomerase trafficking and is essential for the
localization of telomerase RNA both to Cajal bodies and telomeres.”
While all this jargon-filled science may sound difficult to
understand, the discovery could lead to new ways to attack cancers by blocking
their ability to grow. While that is years down the road, the new understanding
of how this crucial biological action in the human body takes place will at the
very least open new avenues of investigation into why and how cancer cells
continue to grow and take the human toll they do every day.
The research was primarily supported by grants from the
National Cancer Institute of the National Institutes of Health.
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