Newly indentified protein linked to cancer cel...( really only the beginning of the story....)

Once the team cloned the gene, however, its similarity to IL-10 and two other related interleukins, IL20 and IL22, was apparent, Liang said. Further research to test binding between IL-24 and the known receptors in the IL-10 family found that IL-24 binds to two different two-part (heterodimeric) receptors, and that it shares a subunit of these receptors with IL-20 and IL-22.

"If they share both sequence homology and receptor subunits, it provides strong molecular evidence that these interleukins are related," Liang said. "As a result, MOB-5 was properly renamed as a new interleukin."

The scientists also demonstrated that IL-24 can promote cell growth or prevent cell death. This was done using hemopoietic mouse cells that must have interleukin-3 (IL-3) to grow and survive. When the cells were made to express IL-24 receptors, in the absence of both Il-3 and IL-24, the cells died. In the absence of IL-3 but the presence of IL-24, the cells continued to live and grow.

Finding that IL-24 can support cell survival, and finding both IL-24 and its receptors in tumor cells, has an important implication, Liang said. This creates what is called an autocinre loop, through which a cell secretes a protein that then binds to a receptor on itself, sending its own signal to its nucleus. "The cell could then fuel its own growth and survival without the checks and balances by the neighboring cells," Liang said.

The next step will be to try to develop molecules to interrupt this autocrine loop, either by intercepting the IL-24 protein outside the cell after it is secreted, or by blocking the receptors so that the protein cannot bind and therefore transmit its signal back into the cell.

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Contact: Cynthia Manley
cynthia.manley@mcmail.vanderbilt.edu
615-936-5711
Vanderbilt University Medical Center
6-Mar-2002