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Cloning of Cancer-Prone Mice from a Melanoma Cell
NA
volume 3 | issue 9
september 2004Pages: 793-793
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Some cancer cell changes can be reversed, cloning study finds
Nature can reset the clock in certain types of cancer and reverse some of the elements responsible for causing malignancy, reports a research team from the Whitehead Institute for Biomedical Research and the Dana-Farber Cancer Institute.
The scientists, led by Rudolf Jaenisch, MD, of the Whitehead Institute, and Lynda Chin, MD, of Dana-Farber, demonstrated this phenomenon by cloning normal mice from an advanced mouse melanoma cell.
"This settles a principal biological question," says Jaenisch, a noted cloning expert. "The epigenetic elements of cancer are reversible; the genetic elements, as expected, are not." The work was reported in the August issue of the journal Genes and Development.
Cells fundamentally become cancerous because of mutations, or adverse alterations, in their genes, and these genetic changes cannot be undone. "Epigenetic" factors don't involve alterations in genes, but are changes in gene activity caused by outside biochemical factors, including the effects of regulatory genes.
"One of the important implications of these findings is that it shows the epigenetic alterations in a cancer cell contribute to the malignant characteristics of the cell," says Chin.
Konrad Hochedlinger and Robert Blelloch, postdoctoral researchers in Jaenisch's lab, studied whether any of these epigenetic influences can be reversed. First, they removed the nucleus from a melanoma cell and injected it into a normal, de-nucleated egg cell (a process known as nuclear transfer). The environment of the normal oocyte, or egg cell, "reprogrammed" the cancer cell's genome (complete set of genes in the nucleus) so that it could start over again and redevelop as a normal embryo.
After the altered egg cell had grown to a multicellular blastocyst stage, Hochedlinger and Blelloch harvested embryonic stem cells from it. The stem cells, which are capable of turning into any kind of cell in the body, were then inserted into healthy mouse blastocysts. Many of these blastocysts later developed into normal adult mice.
Nevertheless, when certain cancer-related genes in these mice were activated, they developed malignant tumors at a much faster rate than the control mice.
According to Chin, a dermatologist and cancer researcher, the research opens up the door to developing animal models of cancer enabling researchers to study the relative contributions of the epigenetic versus genetic lesions in the development of cancer.
"The implication is that if you can use drugs to target the epigenome (the non-genetic cancer-causing factors), you can alter the fate of the tumor cell," says Chin. "This may prove to be a key therapeutic opportunity for diverse cancers."
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.