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A new ground zero for prostate cancer
Date:7/29/2010

hers distinguish luminal cells from basal cells. They then used these markers to separate the two cell types in samples of human prostate tissue. Patients undergoing prostate cancer surgery agreed to donate the tissue for research studies. In those operations, a surgeon typically removes healthy tissue along with the cancer. The tissue from those operations was given to Witte's team to provide the material they needed for their studies.

After separating luminal cells from basal cells, the researchers prodded all of the cells to become cancerous by introducing three genes known to promote prostate cancer. A virus was used to deliver the genes -- called AKT, ERG, and AR into luminal cells and basal cells.

The researchers then separately engrafted the transformed luminal cells and the transformed basal cells into mice. After 16 weeks, none of the luminal grafts had formed tumors. In the meantime, though, the basal cell grafts had gone through three stages: They had grown into prostate-like tubules, transformed into damaged pre-cancerous cells, and then turned malignant and formed tumors. Tellingly, when examined by a pathologist, these tumors looked identical to human prostate tumors, said Andrew Goldstein, a Ph.D. student in Witte's lab and first author on the Science paper.

"In our experimental model, basal cells show the ability to form the disease that looks like what we see in humans," says Goldstein. "We feel very confident that we have recreated something that strongly resembles human prostate cancer. We conclude that basal cells may be a source of the disease in humans."

The engrafted basal cells after turning cancerous also looked very much like luminal cells, as in clinical tumor samples. Witte says that this suggests that on their way to becoming cancerous, basal cells grow into more luminal-like cells. This makes sense, he notes, because the engrafted human basal cells also acted like prostate stem cells, growing into p
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
Source:Eurekalert

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