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Single microRNA causes cancer in transgenic mouse

esearch associate, decided to isolate miR155 function by inserting the gene, along with an enhancer, to promote its expression, into fertilized eggs inside a pregnant mouse. The researchers then screened the offspring to find those that had incorporated miR155 into their genomes and followed them to see what effect miR155 might have.

Within three weeks, the transgenic mice developed greatly enlarged spleens, and after six to seven months, they became sick and died. Offspring that did not express miR 155 did not have enlarged spleens and developed normally.

When Costinean examined the spleens of the transgenic mice more closely, he discovered they were full of immature B cells ?and only immature B cells.

"This is significant, because a proliferation of these precursor B cells is one of the hallmarks of some types of leukemia and lymphoma," he said.

B cells, or lymphocytes, are white blood cells that help the body fight infection.

In humans, they are produced from stem cells in the bone marrow and then evolve through several stages before they become mature enough to create antibodies. Antibodies are proteins that sit on the surface of B cells or that are secreted by B cells that can detect the presence of foreign invaders like bacteria, viruses or parasites.

Lab tests revealed that the B cells in enlarged spleens had stopped evolving in the pre-B phase, right at the point where a B cell normally begins to create structures necessary for antibody development.

"We believe that miR 155 initiated the process that blocked further differentiation of these cells," says Costinean.

Croce says the results are consistent with previous study findings. "We know that miRNAs often act just like oncogenes, in that they promote abnormal cell growth that leads to cancer. Others, however, behave more like tumor suppressors, because they block genes that keep abnormal cell division in check or induce prolonged survi
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Source:Ohio State University


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