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Scientists ID possible cancer-causing gene By Ed EdelsonHealthDay Reporter

Source: HealthDay

(HealthDay News) -- Looking at genes in the lowly fruit fly, researchers say

they've found one that might play a role in human cancer and could become a

target of treatment or prevention.

It's not an outrageous idea, said lead researcher Duojia Pan, whose group

reported the finding in the Aug. 12 issue of the journal Cell. That's because,

on the genetic level at least, humans are remarkably similar to fruit flies.

" Two thirds of the genes in humans are found in fruit flies, " said Pan, an

associate professor of molecular biology and genetics at the s Hopkins

Institute for Basic Biomedical Sciences.

And the fruit fly gene in question, which codes for a protein the researchers

called Yorkie, has a direct counterpart in humans.

That counterpart -- called YAP -- seems to play the same role, suggesting that

in humans, a defect in the gene that makes YAP might contribute to cancer.

In the fruit fly, the Yorkie gene regulates the size of organs, making it a

primary culprit as a cancer-causing gene, Pan said.

" If organ size is not regulated properly, you have cancer, " Pan said, adding

that a mutation in a gene that regulates organ size can cause that kind of

malignant overgrowth.

The new research showed that fruit flies missing a gene called hippo developed

tumors. That research revealed a tumor-suppression pathway involving proteins

made by hippo and two other similar genes, all of which function to chemically

add phosphate to other proteins, a process called phosphorylation, the

researchers said.

" From those results, we predicted that another protein must be involved in the

tumor-suppression pathway that is a target of the phosphorylation cascade, " Pan

said.

That other protein appears to be Yorkie, the researchers said. Pan and his

colleagues showed that phosphorylation could be stopped by adding a phosphate

group to the Yorkie protein. But when the scientists reduced levels of hippo and

other proteins that keep Yorkie in check, the protein caused tissues to keep

growing by triggering more cells to grow and fewer to die -- the hallmarks of

cancer.

Pan is now trying to identify the signal that tells genes like hippo to turn on

or off once an organ grows to the appropriate size.

The Yorkie discovery is the latest in a series of investigations that Pan

started at the University of Texas Southwestern Medical Center at Dallas and is

continuing at s Hopkins.

" That pathway is conserved from fruit fly to mouse to human, " said Jianbin

Huang, an instructor in molecular biology at the Texas center who was a member

of Pan's research team there.

Huang and his colleagues are working with mice to get more details on the

pathway and its possible role in cancer. But he noted that " Yorkie is a homolog

of YAP. "

Pan has moved into studies of the human gene. " We are looking at tissue samples

of cancer cells to see if they express more of this protein than normal cells, "

he said. " We are screening collections of human cancer cells and tissues to see

if there is overexpression. "

If cancer cells are found to produce excess amounts of the YAP protein, the

question then becomes, " is this causative? " Pan said. " If overexpression is

responsible for the cancer, then if we reduce the amount of the protein, we can

reverse the cancer process. "

But the effort to identify the specific genetic signals responsible for cancer

is just beginning, he said.

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More information: The state of the art in cancer genetics is described by the

National Cancer Institute.

For the latest health news & Health-Life Services like tools, calculators, & a

physician locator, go to www.healthday.com.

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