Loss of Keratin 10 Leads to Mitogen-Activated Protein Kinase (MAPK) Activation, Increased Keratinocyte Turnover, and Decreased Tumour Formation in Mice (2004)

Author(s): Reichelt J, Furstenberger G, Magin TM

    Abstract: Keratin 10 (K10) is the major protein in the upper epidermis where it maintains keratinocyte integrity. Others have reported that K10 may act as a tumor suppressor upon ectopic expression in mice. Although K10-/- mice show significant epidermal hyperproliferation, accompanied by an activation of the mitogen-activated protein kinase (MAPK) pathway, they formed no spontaneous tumors. Here, we report that K10-/- mice treated with 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) developed far less papillomas than wild-type mice. BrdU(5-bromo-2'-deoxyuridine)-labeling revealed a strongly accelerated keratinocyte turnover in K10-/- epidermis suggesting an increased elimination of initiated keratinocytes at early stages of developing tumors. This is further supported by the absence of label-retaining cells 18 d after the pulse whereas in wild-type mice label-retaining cells were still present. The concomitant increase in K6, K16, and K17 in K10 null epidermis and the increased motility of keratinocytes is in agreement with the pliability versus resilience hypothesis, stating that K10 and K1 render cells more stable and static. The K10-/- knockout represent the first mouse model showing that loss of a keratin, a cytoskeletal protein, reduces tumor formation. This is probably caused by an accelerated turnover of keratinocytes, possibly mediated by activation of MAPK pathways.

      • Date: 07-10-2004
      • Journal: The Journal of Investigative Dermatology
      • Volume: 123
      • Issue: 5
      • Pages: 973-981
      • Publisher: Nature Publishing Group
      • Publication type: Article
      • Bibliographic status: Published

      Keywords: DMBA epidermis keratin 10 MAPK papilloma


      Dr Julia Reichelt