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Some brain tumors may be mediated by tiny filament on cells
Date:8/23/2009

s.

Han engineered mice to continuously express a mutant form of Smo, known to cause cancers in humans. In these mice, the mutant form of Smo moved to the cilium, independent of Ptch1, driving the development of medulloblastoma. When Han genetically removed the cilium, no tumors developed.

Predicting that continuously activating a protein in the signaling pathway downstream of Smo and primary cilia would induce tumors whether or not the cilium were present, Han activated Gli2 and removed the cilium. To the team's astonishment, all of the mice developed medulloblastoma only when primary cilia were removed.

The explanation may be, the researchers say, that removing the primary cilium prevented it from carrying out one of its other jobs activating proteins in its pathway whose jobs are to suppress Hedgehog signals.

Next, the team examined 38 samples of autopsied brain tissue donated to the UCSF Medical Center Neurological Surgery Tissue Bank and to the Neuropathology Laboratory at St. Jude Children's Research Hospital. Primary cilia were present in most cases of one form of the disease, known as desmoplastic medulloblastoma, and mostly absent in another, known as anaplastic medulloblastoma. Of 24 tissue samples analyzed for their gene-expression profiles, primary cilia were identified almost exclusively in tumors driven by Hedgehog or Wnt signaling.

The findings have prompted the team to begin investigating primary cilia's role not only in other subsets of medulloblastomas but also in glioblastomas, the most common brain tumor in adults, with an eye toward identifying a diagnostic strategy and therapeutic targets.

More broadly, they are considering other questions. Most cells have a primary cilium, notes Alvarez-Buylla. "I think people have paid little attention to this thin, cellular extension or have thought of it just as a remnant of a ciliated organism. It's become clear that it's much more fascinating than that: It may play crit
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

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