X-Message-Number: 23961
Date: Thu, 22 Apr 2004 23:21:15 -0700 (PDT)
From: Doug Skrecky <>
Subject: Downregulating Foxm1b growth gene as anticancer strategy


Researchers Discover Gene That Causes Liver Cancer In Animals

When the gene, called Foxm1b, was deleted from liver cells in laboratory
mice, the animals failed to develop tumors. Even when the researchers
attempted to induce the formation of these tumors artificially, using a
standard laboratory technique, the mice remained cancer free.

"To my knowledge, this is the first time a gene has been directly linked
to the growth of cancer cells in live animals," said Robert Costa,
professor of biochemistry and molecular genetics in the UIC College of
Medicine and the lead investigator in the study.

Results of the study are published in today's issue of Genes and
Development, the premier peer-reviewed journal on molecular genetics and

Earlier studies had shown that Foxm1b is crucial for tissues to repair
and replenish themselves -- a finding that led Costa to dub it the
"fountain-of-youth gene." When it is absent, the genetic instructions
inside a cell, called DNA, don't duplicate and cells have trouble

Foxm1b, which is stimulated by growth hormone, appears to malfunction in
old age and in certain rare diseases that cause premature aging. It is
one of a family of genes that controls the entire life cycle of a cell,
including its proliferation, maturation and death.

In the current study, scientists in Costa's lab used genetically altered
mice to establish the link between Foxm1b and liver cancer, showing that
the gene is essential for the cancerous cells to multiply.

"Foxm1b is expressed in many different kinds of cancer cells, which
leads us to believe it plays a key role in promoting the growth of
tumors other than liver cancer," Costa said.

The scientists also created a prototype for a drug that would block
Foxm1b activity and starve tumor cells of the protein that Foxm1b
manufactures, preventing their multiplication.

The potential drug was a variant of a protein known to suppress tumors,
called p19ARF. By attaching a string of arginines, a component of
proteins, to a segment of p19ARF that was shown to inhibit Foxm1b, the
scientists enabled the tumor suppressor to cross the cell membrane and
enter the body of the cancer cells.

"The 'drug' reduced not only the activity of Fox m1b but also the growth
of cancer cell colonies," Costa said. "We're extremely excited about
this finding because it suggests we might have a therapy for stemming
the spread of liver cancer."

Costa, who has made a career of studying the Fox family of genes, has
long puzzled over why Foxm1b is not active in old age. When the gene is
out of commission, tissues can't regenerate, muscles atrophy, and bones
thin. For an organism subject to rules of natural selection, the
suppression of Fox m1b seemed odd.

With the current findings, however, Costa wonders whether the human body
has evolved to curb Foxm1b in old age in an attempt to thwart cancer.

"I know it's speculative," Costa said, "but perhaps aging is just an
unintended by-product of an adaptive mechanism to stave off cancer and
certain death. Perhaps aging is just nature's way of attacking cancer."

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