title: A new link between epigenetic progenitor lesions in cancer and the dynamics of signal transduction.
abstract: Our recent study of the mechanism by which an epigenetic alteration, loss of imprinting (LOI) of Igf2, increases tumor risk, revealed a strong relationship between IGF2 dosage, the dynamics of signaling along the IGF2 axis, cell proliferation and tumor risk.(1) Colon epithelia in a mouse model with LOI of Igf2 showed increased sensitivity to IGF1R blockade and abrogation of premalignant lesion development in LOI(+) mice. These results are consistent with the epigenetic progenitor model of cancer,(2) in which epigenetic changes precede and heighten risk of cancer in response to oncogenic mutations. Thus, one can envision a highly targeted and focused chemoprevention strategy targeted to signaling pathways in nonmalignant cells that have undergone an epigenetic lesion, rather than a broad approach toward reversing epigenetic lesions that may have unintended consequences affecting the whole epigenome.
authors.affiliation: Department of Medicine, Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Winston
authors.initials: W
authors.lastname: Timp
authors.forename: Andre
authors.initials: A
authors.lastname: Levchenko
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin; D007335:Insulin-Like Growth Factor II