SAN DIEGO--So little is known about cell cycling that a new study on
a possible mechanism for why cells fail to exit the cell cycle was termed
the "most exciting presentation" of the American Association
for Cancer Research's 88th annual meeting. Stephen H. Friend, MD, of the
Fred Hutchinson Cancer Research Center, made the comment at a press briefing
held at the meeting.
The research, from the Cell Biology and Metabolism Branch of the NIH's
National Institute of Child Health and Human Development, led by NCI director
Richard Klausner, MD, involves the mechanism of action of the von Hippel-Lindau
(VHL) tumor suppressor gene. The inactivation of this gene is associated
with both von Hippel-Lindau disease and sporadic kidney cancer.
The NIH scientists, Arnim Pause, PhD, and Stephen Lee, PhD, studied
the effect of growth factor withdrawal on kidney cells that were positive
or negative for production of the protein produced by the VHL gene (pVHL).
They found that the cells that produced pVHL exited the cell cycle and
entered the quiescent G0 phase after growth factor withdrawal. In contrast,
the pVHL-negative kidney cancer cells failed to leave the cell cycle, instead
continuing through several replication cycles, a process thought to initiate
tumor formation. "These observations suggest that pVHL is regulating
the ability of cells to enter quiescence in response to growth factor withdrawal,
and might explain why the VHL gene has a gatekeeper function in the kidney,"
Dr. Pause said. "The VHL protein might be part of a pathway that is
disrupted in many types of cancer."
The research is especially exciting, Dr. Friend said, as it relates
to cytotoxic cancer treatments. "If you were to ask how many physicians
in the audience had ever seen a case of von Hippel-Lindau disease, it's
probably one in a hundred or less," Dr. Friend said, "and yet
by studying this rare genetic disease, the NCI researchers came upon a
clue that may be pivotal to understanding why cancer therapies don't work
better than they do."
When treating cancer, he noted, "we want all of the cells to be
cycling because in that instance, we can actually treat all of them. It's
the quiescent ones that don't give themselves up to be killed that stay
around and cause trouble."
Rather than labeling the research a major cancer breakthrough, Dr. Friend
called it "the type of clue that in the past has led to breakthroughs."
He suggested that many scientists were inspired by the von Hippel-Lindau
gene presentation. "I think everyone left the meeting thinking, What
experiments can I do that might take advantage of this new knowledge."