This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wilke, M. S. Articles by Scott, R. E. Search for Related Content PubMed PubMed Citation Articles by Wilke, M. S. Articles by Scott, R. E.

American Journal of Pathology, Vol 131, 171-181, Copyright © 1988 by American Society for Investigative Pathology

REGULAR ARTICLES

Biologic mechanisms for the regulation of normal human keratinocyte proliferation and differentiation

MS Wilke, BM Hsu, JJ Wille Jr, MR Pittelkow and RE Scott
Section of Experimental Pathology, Mayo Clinic/Foundation, Rochester, Minnesota 55905.

Normal human keratinocytes can be grown in serum-free medium, and the integrated control of their proliferation and differentiation can be modulated experimentally. The growth of cultured human keratinocytes can also be specifically arrested at either reversible or irreversible growth arrest states. Reversible growth arrest is induced by culture in medium containing TGF-beta or ethionine or in medium deficient of isoleucine. Irreversible growth arrest is induced by culture in razoxane-containing medium or by routine passage of keratinocytes until senescence results. The current studies were performed to determine from which growth arrest states keratinocyte differentiation occurs. Cells were therefore growth-arrested at each state, and they were then incubated in several different differentiation-promoting culture conditions. The results show that differentiation, as determined by morphologic, cytochemical, and immunofluorescent assays, can be induced from multiple reversible and irreversible growth arrest states by a series of complex biologic mechanisms. More specifically, at least three distinct stages appear to be involved in the process of keratinocyte differentiation. First, cells arrest their growth at a reversible predifferentiation state. Second, cells irreversibly lose their proliferative potential. Finally, cells express the terminally differentiated keratinocyte phenotype.

This article has been cited by other articles:

				T. Kawakita, E. M. Espana, H. He, R. Smiddy, J.-M. Parel, C.-Y. Liu, and S. C. G. Tseng Preservation and Expansion of the Primate Keratocyte Phenotype by Downregulating TGF-{beta} Signaling in a Low-Calcium, Serum-Free Medium Invest. Ophthalmol. Vis. Sci., May 1, 2006; 47(5): 1918 - 1927. [Abstract] [Full Text] [PDF]

				R. Mazzieri, V. Jurukovski, H. Obata, J. Sung, A. Platt, E. Annes, N. Karaman-Jurukovska, P.-E. Gleizes, and D. B. Rifkin Expression of truncated latent TGF-{beta}-binding protein modulates TGF-{beta} signaling J. Cell Sci., May 15, 2005; 118(10): 2177 - 2187. [Abstract] [Full Text] [PDF]

				W. Ding, M. M. Witte, and R. E. Scott Transformation Blocks Differentiation-induced Inhibition of Serum Response Factor Interactions with Serum Response Elements Cancer Res., August 1, 1999; 59(15): 3795 - 3802. [Abstract] [Full Text] [PDF]

				J. J. LaPres and L. G. Hudson Identification of a Functional Determinant of Differentiation-dependent Expression in the Involucrin Gene J. Biol. Chem., September 20, 1996; 271(38): 23154 - 23160. [Abstract] [Full Text] [PDF]

				K. Schallreuter, J. Wood, M. Pittelkow, M Gutlich, K. Lemke, W Rodl, N. Swanson, K Hitzemann, and I Ziegler Regulation of melanin biosynthesis in the human epidermis by tetrahydrobiopterin Science, March 11, 1994; 263(5152): 1444 - 1446. [Abstract] [PDF]