An Enzyme that Holds the Key to Immortality
Hopkins Researchers, searching for an Achilles heel --
for any tiny chink in prostate cancer's impressive
armor -- believe they've found a promising candidate in
a fascinating enzyme called telomerase.
Donald S. Coffey, Ph.D., Director of Research
Prostate cancer is a fearsome foe, whose worst cells are,
for all practical purposes, immortal -- utlimately impervious to treatment,
once cancer has spread to the lymph nodes or bone.
But Hopkins researchers, searching for an Achilles heel -- for any
tiny chink in prostate cancer's impressive armor -- believe they've
found a promising candidate in a fascinating enzyme called telomerase.
One day, understanding what this enzyme does may unlock riddles far
beyond the prostate -- perhaps even expanding our grasp of how the body
ages, and why it does.
And one day, cracking its mysteries may enable scientists to turn prostate
cancer into vulnerable -- and killable -- mortals again.
"Every cell in the human body ages, and after a specific number of
divisions, dies," says Donald S. Coffey, Ph.D., director of research.
"Only the cancer cell has broken through this aging barrier. This means
that these cells are capable of dividing on, and sustaining
Think of a normal cell as a candle with a wick; in this case, the wick
is a long strand of DNA. With every cell division, this wick shrinks
a little; it loses a small piece of DNA. When this wick becomes too
short, the cell dies. "This provides the counting mechanism for the
biological clock," Coffey explains.
But in cancer cells, the wick doesn't get any shorter -- because of
telomerase: This enzyme keeps replacing the DNA at the end of the
strand, so there's not countdown. Like Dorian Gray, the cell never
Coffey and colleagues have shown that telomerase is active in human
prostate cancer cells, making them immortal. But it's not
switched on in BPH (benign prostatic hyperplasia), and in normal
Say you have a manuscript, says Coffey, "and on the front and back of
the manuscript, you have 50 white, blank pages." The blank pages
are filler -- meaningless, repetitive chunks of DNA that act as cushions
for the really important part, the fragile genes inside. "Each time
you go into the xerox room, you lose one of these pages. Every time
you make a copy of the manuscript -- in other words, a new cell --
you lose a page. After you lose it down to a certain length, the cell
becomes unstable and dies, and that's aging.
"Now, in cancer, somebody stands at the door of that room, and each time
you go in, adds a new sheet onto the front and back." So for every
sheet lost, one is gained, and the cell remains stable. "The white,
blank pages are telomeres, the repetitive DNA at the end of each
chromosome, and that person standing at the door is telomerase."
Coffey and colleague Alan Meeker are using a highly sensitive assay that
can detect telomerase in as few as 10 cells, and works in needle
biopsies of the prostate. Why is this important? Because currently,
needle biopsies -- although much improved in recent years -- don't always
give definitive answers. Sometimes the needle misses the cancer;
sometimes what's under the microscope is almost impossible to label
definitely as cancer. And even if cancer is seen in a few cells, is it
the "good kind," so-called "incidental" cancer that, in millions of men,
doesn't do much, but just sits in the prostate for decades? (In other
words, could a telomerase test help determine if a man can afford to wait
on treatment?) Or is the "bad" kind, cancer that needs to be treated
as soon as possible? One days, Coffey speculates, a telomerase assay may
mark cells that are not only cancerous, but "on the march" -- and
potentially headed out of the prostate. Such a test may take much of the
confusion out of many treatment decisions.
Even more exciting: If somehow telomerase could be blocked -- so cancer
cells age and die like other cells -- then this might even be a way to
make even advanced cancer curable one day. Says Coffey: "This could
be an important target for future therapy."
"Telomerase Activity, a Prevalent Marker of Malignant Human Prostate
Cancer," Cancer Research, Vol. 56, p. 218, 1996. H.J.
Sommerfeld, Alan Meeker, Donald S. Coffey, et al.