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Discovery of Two-Faced Gene
By W&M Researcher May Yield Cancer Clues
(WILLIAMSBURG, VA) -- The discovery of the "two-faced" gene Pax-5 by a
William and Mary research is yielding tantalizing new clues about the
genesis of some types of cancer. Pax-5 is a member of a group of genes
that have the unusual ability to produce multiple proteins with many
different functions, some of which may lead to cancer, says Assistant
Professor of Biology Patty Zwollo.
Zwollo didn't realize the full significance of her discovery until
she started getting phone calls from cancer researchers throughout the
nation. They called to request reprints of her paper that had appeared in
The Journal of Biological Chemistry detailing her discovery about an
unusual gene called Pax-5.
"Pax-5 has been connected to certain types of lymphoma," said
Zwollo. "Now these scientists are thinking it may also be involved with
other forms of cancer."
What sparked the researchers' interest in Zwollo's work was her
finding that Pax-5, which plays a vital role in normal cell proliferation,
produces at least four different proteins instead of only one as previously
thought.
Nearly all processes essential to life are regulated by proteins
that are formed and released as a result of gene activity. Sometimes, for
often inexplicable reasons, genes will produce too much or too little of a
particular protein, causing a range of effects -- the most detrimental
being the uncontrolled multiplication of cells. An abnormally functioning
Pax-5 has already been connected to one form of cancer and may be involved
in others.
First identified in sea urchins and thought to exist in all
animals, Pax-5 is particularly instrumental during embryonic development.
Scientists believe it plays a role in the formation of the immune system,
but are uncertain of the mechanisms involved in this process.
This mystery has been compounded by Zwollo's discovery recently of
the new proteins. While most genes produce only one protein with a distinct
function, Pax-5 is among a group of genes that have the unusual ability to
produce multiple or "alternative-spliced forms" of proteins with many
different functions.
Scientists know that at least one of the Pax-5 proteins activates
processes that allow cells to multiply. Oddly, studies also suggest that
another of the Pax-5 proteins suppresses cell proliferation. This
ambivalence fascinates researchers like Zwollo for its potential
implications.
"We are only beginning to understand the relationship among these
proteins and whether they act individually or together," explained Zwollo,
who first became interested in Pax-5 while studying a related gene at Johns
Hopkins University. "What we suspect is that if Pax-5 turns on at the wrong
time and causes an imbalance in the protein levels, cells begin multiplying
when they're not supposed to."
Zwollo hopes to begin shedding light on this conundrum over the
next few months. She's finishing a $250,000 grant from the National Science
Foundation which funded her preliminary research and is hoping to secure
additional support from NSF by the end of the year.
"My early research was focused on identifying the proteins and
their structure," said Zwollo. "Now I want to look at their function."
To accomplish that, Zwollo is planning a series of experiments with
transgenic mice whose Pax-5 gene has been altered to overproduce one of the
proteins. "This will allow us to observe the effect of each of the proteins
more directly and hopefully pin down their functions," she said.
Once the proteins' functions are better understood, Zwollo believes
that it may be possible in the very long term to develop a "gene therapy"
for cancers arising from a malfunctioning Pax-5.
Zwollo has already enlisted several biology concentrators in her
research, and plans to collaborate with geneticists at the Medical College
of Virginia, the University of Virginia, and in her own department who have
worked with genes similar to Pax-5.
Despite the significance of her early findings, Zwollo is
circumspect about the potential applications of her research.
"There are so many variables involved in cancer that it's often
impossible to single out any one as the source," she said. "We're a long
way from determining how much of a role Pax-5 has in the growth of some
cancers. But often times, some of the most basic research involving the
disease starts in labs like mine."
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