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Jeff Sutherland

Twice the Energy with Half the Stress

Cancer: It’s a Programming Problem/Opportunity

When I published my Ph.D. thesis on mathematical modeling of carcinogenesis in 1980 (see previous postly) a fundamental presumption was that programs exist in the DNA that cause cancer when triggered. This view was controversial then. Today it is the conventional point of view. It has taken over 20 years to zero in on the exact means of reprogramming the cells. Surprisingly, the same mechanisms that cause cancer can be use to stimulate adult stem cells to regrow human tissues. The future of tranplant medicine is avoiding transplants completely by reprogramming cells to regrow human organ systems in the body.

The entire issue of a recent issue of the Journal of Biology is focussed around a single “hot” paper on this topic. Julie Clayton gives an overview.

Wnt signaling and the developmental fate of lung cells

Julie Clayton

Journal of Biology 2004, 3:9

28 June 2004© 2004 BioMed Central Ltd

When embryologists began cutting and pasting pieces of chick embryos into new positions back in the 1950s and 1960s they sometimes noticed bizarre changes in tissue types but had little notion of what was going on at a molecular level, and even less idea of how to investigate it. Likewise, clinicians have puzzled for many years over pre-cancerous conditions called metaplasias, in which cells appear in one part of the body that normally belong in another. Neither group could get a handle on how cells escape the usual ‘rules’ that tell them which types of tissue to form in which part of the body. Now, researchers from Duke University Medical Center have contributed to a new awareness of the molecular signals that could explain these phenomena; furthermore, their data suggest possible ways to manipulate stem cells of adult tissues, to make them develop into the tissue of choice for therapeutic purposes.

Tadashi Okubo and Brigid Hogan report in this issue of Journal of Biology a surprising result from their studies of the Wnt signaling pathway, a central cell-cell signaling pathway during development. If a key component of this pathway is expressed in active form in the lungs of developing transgenic mouse embryos, cells appear within the lung that are more like cells of the gut than they are like their lung neighbors.

The lung cells in the transgenic mice seem to have switched developmental pathways to become part of a different lineage; the lungs appear grossly normal at first, but they contain far fewer than normal of the usual fully differentiated lung cell types. By microscopy alone it was initially hard to say what had happened to the specialized lung cells that should have lined the airways and alveoli, but gene-expression profiling using microarrays revealed the activity of genes that are normally expressed only in intestinal epithelial cells.

“We nearly fell off our chairs when we saw all these intestinal genes coming up,” says Hogan.