MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY
The Expression of Keratin K10 in the Basal Layer of the Epidermis Inhibits Cell Proliferation and Prevents Skin Tumorigenesis*

https://doi.org/10.1074/jbc.M201001200Get rights and content
Under a Creative Commons license
open access

Forced expression of K10, a keratin normally expressed in postmitotic, terminally differentiating epidermal keratinocytes, inhibits the progression of the cell cycle in cultured cells (Paramio, J. M., Casanova, M. Ll., Segrelles, C., Mittnacht, S., Lane, E. B., and Jorcano, J. L. (1999) Mol. Cell. Biol. 19, 3086–3094). This process requires a functional retinoblastoma (pRb) gene product and is mediated by K10-induced inhibition of Akt and PKCζ, two signaling intermediates belonging to the phosphoinositide (PI) 3-kinase signal transduction pathway (Paramio, J. M., Segrelles, C., Ruiz, S., and Jorcano, J. L. (2001)Mol. Cell. Biol. 21, 7449–7459). Extending earlier in vitro studies to the in vivo situation, this work analyzes the alterations found in transgenic mice that ectopically express K10 in the proliferative basal cells of the epidermis. Increased expression of K10 led to a hypoplasic and hyperkeratotic epidermis due to a dramatic decrease in skin keratinocyte proliferation in association with the inhibition of Akt and PKCζ activities. The inhibition of cell proliferation and Akt and PKCζ activities was also observed although to a minor extent in low hK10-expressing mice. These animals displayed no overt epidermal phenotype nor overexpression of K10. In these non-phenotypic mice, ectopic K10 expression also resulted in decreased skin tumorigenesis. Collectively, these data demonstrate that keratin K10 in vivo functions include the control of epithelial proliferation in skin epidermis.

Cited by (0)

Published, JBC Papers in Press, March 11, 2002, DOI 10.1074/jbc.M201001200

*

This work was partially funded by Grant PB94-1230 from the Spanish DGICYT (Dirección General de Investigación Cientı́fica y Tecnológica). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§

Both authors contributed equally to this work.