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U-M scientists find genes that control growth of common skin cancer

n. In addition, the researchers found that sustained expression of Gli2 is necessary for the continued growth of these tumors. When Dlugosz and colleagues turned Gli2 off, the BCC tumor cells stopped growing and were eliminated by a programmed cell death process. These results are consistent with previous work from other labs studying different Hh-associated tumors, “but we were very surprised to see that some tumor cells persisted after shutting down Gli2 expression,?said Dlugosz. In some of the regressed tumors Gli2 reactivation leads to resumption of BCC tumor growth, suggesting that the residual cell populations may represent BCC tumor stem cells, but Dlugosz cautions that there is as yet no definitive evidence that tumor stem cells exist in BCC. In additional studies, the researchers found that regressing BCC cells could be reprogrammed to differentiate into various epithelial cell types, ultimately capable of assembling fully-formed hair follicles. These results suggest that BCCs contain cells capable of multi-lineage differentiation, similar to normal hair follicle stem cells from which they may arise. If the results of this study are applicable to human BCC, the discovery of residual tumor cells and tumor recurrence may be particularly important given the current efforts to develop Hh pathway inhibitors as a means of combating human BCCs, as well as other cancers. In contrast to other cancer models where inhibition of Hh signaling leads to durable tumor regression, Dlugosz's new work raises the possibility that Hh pathway inhibition in BCCs, while effectively diminishing tumor size, may not be curative due to the survival of this residual tumor cell population. “Our work demonstrates that BCC growth in this model remains strictly dependent on the Hh pathway,?says Mark Hutchin, M.D., a U-M resident in dermatology and lead author on the paper. This is different from many other genetic mouse models of cancer, in which tumor regression following inhibition of an
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Source:U-M Medical School


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