Reprogramming Cancer Cells

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Science  27 Aug 2004:
Vol. 305, Issue 5688, pp. 1214
DOI: 10.1126/science.305.5688.1214a

An anguished Lady Macbeth says, “What's done cannot be undone.” Does this apply to cancer cells?

Cancer arises as a result of both genetic and epigenetic modifications. Whereas genetic changes permanently alter the DNA sequence of the tumor cell, epigenetic changes act more subtly—for example, by altering the way that critical proteins are packed around DNA. The extent to which these reversible epigenetic changes contribute to tumorigenesis is poorly understood.

In two studies, investigators have examined whether cancer cells can be reprogrammed into a normal state by transferring nuclei from mouse tumor cells into enucleated mouse oocytes and then assaying their ability to direct early embryo development. Blelloch et al. found that transfer of nuclei from embryonal carcinoma cells resulted in normal blastocysts from which embryonic stem (ES) cells could be produced, but the ES cells had the same tumorigenic potential as the donor cells. Hochedlinger et al. likewise found that nuclei from many tumor cell lines could not be reprogrammed. One remarkable exception, however, was a melanoma cell line whose nucleus not only produced ES cells, but was able to direct the full development of an adult mouse. These results underscore the important role of genetic changes in tumor development, but raise the possibility that in certain tumor types, epigenetic changes may play a predominant role. — PAK

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.0405015101 (2004); Genes Dev. 18, 1875 (2004).

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