Theory Lunch this week
October 6, 2010 § Leave a comment
How does the first cell in a tumor behave?
Friday, 8 Oct 2010, 12pm
Warren Alpert 563 – HMS
Cavendish Laboratory of Physics, Cambridge, and
Department of Systems Biology, HMS
UV B (UVB) radiation induces mutations to the p53 tumor suppressor gene, leading to skin cancer. How do the earliest p53 mutant cells behave? Do these cells already disrupt homeostasis? In this talk I will discuss how clone size statistics from mice and humans exposed to UVB radiation discloses the growth dynamics of p53 mutant clones . The data show that p53 mutation leads to excess cell proliferation very early on; but ending UVB exposure rebalances p53 mutant behaviour. This has implications for deciding how to plan your time on the beach: ongoing low-intensity UVB radiation increases the number of precancerous cells dramatically compared with sporadic, higher-intensity exposure at the same cumulative dose. Repeating these experiments with several transgenic mice provides hints of the mechanism underlying loss of homeostasis in p53 mutant cells.
1. A M Klein, D E Brash, P H Jones, B D Simons, “Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia”, PNAS 107:270-275 2010. PubMed