UCLA researchers test new cancer model
By Jennifer Lauren Lee
Nov. 12, 2002 9:00 p.m.
UCLA researchers may soon be able to coax human genes into
stopping a cancer before it starts.
Scientists at UCLA’s Jonsson Cancer Center have created a
genetically engineered breed of mice which they can now use to test
drugs to combat three common types of lymphoma. These cancers claim
the lives of 26,000 Americans each year, according to the American
Cancer Society.
“People have been trying for a long time to develop a
model to study this type of lymphoma,” said Dr. Mike Teitell,
a physician and researcher at UCLA’s Jonsson Cancer Center,
and lead author of the article published about this study.
However, previous animal models have never been able to catch
the cancer at the stage of development that usually afflicts
humans, according to Teitell.
In many of these previous models, the cancer would develop so
quickly that it would kill the animal before scientists had a
chance to identify the mechanism that was causing the disease,
Teitell said.
But the new animal model designed by UCLA scientists is “a
better model for the cancers that humans have,” he said.
“It’s the most accurate model to date.”
The immune systems of both mice and men contain lymphatic
tissue, which helps the body fight off infection, according to Dr.
Samuel French, a member of Teitell’s research team.
Located in such areas as the tonsils, spleen, and lymph nodes,
lymphatic tissue houses “B-cells.” These specialized
cells produce the antibodies that help our bodies defend themselves
against microscopic foreign invaders like bacteria.
The new study suggests that a single TCL-1 gene is responsible
for the tumors.
“The normal function (of TCL-1) is to protect
cells,” Teitell said.
The gene TCL-1 is found in every cell in your body, but it is
usually activated, or “expressed,” only in certain
situations. For example, when it is expressed in B-cells, TCL-1
acts as a “disguise” that protects the B-cell from the
body’s own defense mechanisms.
However, when a genetic mutation causes TCL-1 to be activated at
the wrong time, a harmful B-cell, which the body has marked for
destruction, can “hide” and make copies of itself along
with the normal B-cells, according to French.
“We (had previously) identified (this) gene by comparing
AIDS-associated lymphomas with non-AIDS-associated
lymphomas,” French said.
He and his collaborators had screened patients both with and
without AIDS to see if there was a connection between the
abnormally expressed TCL-1 gene and these types of cancer.
Their results: with or without AIDS, every patient who had one
of the tumors also expressed the TCL-1 gene at the wrong time.
Teitell and his team, which also includes Microbiology,
Immunology & Molecular Genetics professor Randolph Wall and
graduate student Katrina Hoyer, genetically engineered mice to
express the TCL-1 gene in their B-cells, thereby mirroring the
conditions that the team has seen in patients with these
lymphomas.
“(The mice) are genetically engineered to continually
express TCL-1 in the lymphocytes (cells of the lymphatic
tissue),” Teitell said. “We’re basically letting
the mouse make its own tumors.”
Now that they have identified the gene responsible for these
cancers, the next step for Teitell and his research team is to
determine how TCL-1 causes those cancers, and how its interactions
with other molecules can be blocked.
“(The study) also provides a powerful animal model for
testing drugs that might be used to treat lymphoma,” Wall
said.
The team is currently trying to find out if abnormally expressed
TCL-1 genes are responsible for other human cancers as well.
