50 whys to look for genes: 24. Manipulate enzyme levels related to cancer progression

New research on an enzyme [PAD2] linked to cancer development shows that 37 percent of mice that produce excessive quantities of the enzyme developed skin tumors within four to 12 months of birth, and many of these growths progressed to highly invasive squamous cell carcinoma, a common form of skin cancer.

This research built on earlier work suggesting

 that PAD2 is found at high concentrations in several tumor types, but it was not known whether these elevated levels of the enzyme were causing cancer or merely a consequence of tumor progression. (Buckley 2014)

Moreover, because PAD2 levels are high when there is inflammation this research bolsters the idea that inflammation is involved in the development — or at least the progression of cancer.  If the results shown in these mice apply to humans as well, then “further studies aimed at using PAD2 inhibitors to block carcinoma progression in humans” may be warranted.


Are mice a good model for humans?  A 2010 European Union workshop report ended on an optimistic note, even though “many drugs work well in preclinical trials in mice but turn out to be ineffective when used in clinical trials on humans” and “Most mice used in research are rather young, yet many of the diseases that are of greatest interest to researchers (such as cancer and heart disease) are most common among the elderly,” and “researchers investigating the genetic aspects of disease need to take environmental factors
(e.g. nutrition, infectious diseases, stress and exercise levels) into account.” Some longstanding mice researchers are more skeptical — “Researchers in the United States and abroad were drawing the bulk of their conclusions about the nature of human disease—and about Nature itself—from an organism that’s as divorced from its natural state as feedlot cattle or oven-stuffer chickens.” (Engber 2011).

Buckley, M. (2014) Gene linked to development of skin cancer in mice, http://www.news.cornell.edu/stories/2014/09/gene-linked-development-skin-cancer-mice

Engber, D. ( 2011) The Mouse Trap: The dangers of using one lab animal to study every disease http://www.slate.com/articles/health_and_science/the_mouse_trap/2011/11/lab_mice_are_they_limiting_our_understanding_of_human_disease_.html

E.U. Workshop Of mice and men – are mice relevant models for human disease?  http://ec.europa.eu/research/health/pdf/summary-report-25082010_en.pdf


(Introduction to this series of posts)


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