Alvaro Macieira-Coelho's Developmental biology of neoplastic growth PDF

By Alvaro Macieira-Coelho

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Science 293:2080–2084 Chen CH, von Kessler DP, Park W, Wang B, Ma Y, Beachy PA (1999) Nuclear trafficking of Cubitus interruptus in the transcriptional regulation of Hedgehog target gene expression. Cell 98:305–316 Chen JK, Taipale J, Cooper MK, Beachy PA (2002a) Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev 16:2743–2748 Chen JK, Taipale J, Young KE, Maiti T, Beachy PA (2002b) Small molecule modulation of Smoothened activity. Proc Natl Acad Sci USA 99:14071–14076 Chuang PT, McMahon AP (1999) Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein.

While in vitro focus formation assays in fibroblasts have shown that the A441G mutation promotes the transforming capacity of Tiam1 (Engers et al. 2000), the relevance of the mutation in vivo remains to be determined. To further investigate the contribution of Tiam1 to the formation and progression of tumors in vivo, Tiam1-deficient mice were generated. As expected, these mice displayed reduced Rac1 activity, and were resistant to the development of Ras-induced skin tumors (Malliri et al. 2002).

5 Future Prospects An impressive amount of knowledge about the involvement of Hh signaling in tumor formation and growth has accumulated since the discovery of PTCH as the disease gene in NBCCS. While the research so far has uncovered many important aspects and laid the foundation for the development of potential anti-cancer drugs, many questions are still unanswered and several surprises can probably be expected. The Hh signaling pathway is well described and most of the major players have probably been found.

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