Penn researchers find role for microRNAs in an...( in the Thomas-Tikhonenko lab. In the...)

in the Thomas-Tikhonenko lab. "In the incubator, the cancer cells grow at normal rates, but in the mouse model you see them recruiting a lot of blood vessels and really taking off. Curiously, this is not the case with some other oncogenes. So, what makes MYC special?"

The MYC protein is known to have a role in determining how certain genes are transcribed into messenger RNAs. To understand the role of MYC in angiogenesis, the Penn researchers used microarray technology to screen MYC-positive and MYC-negative cancerous cells for the presence or absence of 192 known pro- and anti-angiogenesis molecules. They found that, while MYC did not lead to excessive amounts of pro-angiogenesis molecules, it did seem to depopulate an entire family of anti-angiogenesis molecules related to the so-called thrombospondin-1 protein. MYC effectively disabled the brakes that slow angiogenesis.

The Thomas-Tikhonenko lab had previously demonstrated that MYC decreases the lifespan of the messenger RNA encoding thrombospondin. Since microRNAs had emerged as important regulators of messenger RNA stability, the Penn researchers believed there was a good chance of a MYC-microRNA-thrombospondin connection.

Their long-standing collaborator Chi Dang, a professor at Johns Hopkins University, suggested talking to another Hopkins researcher, Joshua Mendell. Mendell had extensive expertise in microRNA function and just a few months ago teamed up with Dang to identify MYC as an important regulator of microRNAs. The new collaboration between the Thomas-Tikhonenko and Mendell laboratories identified a missing link between MYC and thrombospondin, which indeed turned out to be a microRNA cluster designated miR-17-92. In the key experiment the researchers engineered poorly angiogenic tumor cells to produce copious amounts of miR-17-92. These modified cells, just like cells with hyperactive MYC from earlier experiments, formed much larger tumors with better blood supplies. <
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Contact: Greg Lester
glester@pobox.upenn.edu
215-573-6604
University of Pennsylvania
31-Jul-2006

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