Cell Growth & Differentiation, Vol 8, Issue 9 989-997, Copyright © 1997 by American Association of Cancer Research

ARTICLES

Modulation of keratinocyte growth factor receptor expression in human cultured keratinocytes

C Marchese, M Sorice, C De Stefano, L Frati and MR Torrisi
Istituto Nazionale Ricerca sul Cancro di Genova, Sezione di Biotecnologie, Rome, Italy.

Keratinocyte growth factor (KGF) belongs to the fibroblast growth factor (FGF) family, and its activity seems to be restricted to epithelial cells. It elicits its biological effects through binding to the KGF receptor (KGFR), a splicing transcript variant of FGF receptor 2 (FGFR2). The presence of multiple isoforms of FGFR2 and the overlapping specificities of the FGFs with respect to their receptors do not allow the use of anti-FGFR antibodies as specific immunocytochemical tools. Here we used a chimeric protein recently obtained by the fusion of KGF to the HFc portion of immunoglobulin G (La Rochelle et al., J. Cell Biol., 129: 357-366, 1995) to analyze the expression and distribution of KGFRs in human keratinocytes cultured in chemically defined medium and incubated with different Ca2+ concentrations to modulate their differentiation. We observed at both immunofluorescence and electron microscopic levels and by Western blot analysis of proliferation (K6) or differentiation (K1) markers that KGFR expression is up-modulated during keratinocyte differentiation. Cytofluorimetric and Western blot analysis revealed that exposure to the high Ca2+ differentiation signal resulted in a significant increase in KGFRs. RNase protection assay using a KGFR-specific cDNA probe demonstrated that this effect was correlated with a > 4-fold increase in KGFR transcript level. Our results suggest that the expression of KGFR, unlike that of the epidermal growth factor receptor, may control the proliferative-differentiative program from basal to suprabasal cells in human skin.

This article has been cited by other articles:

				N. Maas-Szabowski, A. Starker, and N. E. Fusenig Epidermal tissue regeneration and stromal interaction in HaCaT cells is initiated by TGF-{alpha} J. Cell Sci., July 15, 2003; 116(14): 2937 - 2948. [Abstract] [Full Text] [PDF]

				S.J. Das, H.N. Newman, and I. Olsen Keratinocyte Growth Factor Receptor is Up-regulated in Cyclosporin A-induced Gingival Hyperplasia J. Dent. Res., October 1, 2002; 81(10): 683 - 687. [Abstract] [Full Text] [PDF]

				H.-D. Beer, C. Munding, N. Dubois, C. Mamie, D. Hohl, and S. Werner The Estrogen-responsive B Box Protein. A NOVEL REGULATOR OF KERATINOCYTE DIFFERENTIATION J. Biol. Chem., May 31, 2002; 277(23): 20740 - 20749. [Abstract] [Full Text] [PDF]

				Y. Zhang, H. Wang, S. Toratani, J. D. Sato, M. Kan, W. L. McKeehan, and T. Okamoto Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis PNAS, September 13, 2001; (2001) 191377098. [Abstract] [Full Text] [PDF]

				A. Capone, V. Visco, F. Belleudi, C. Marchese, G. Cardinali, M. Bellocci, M. Picardo, L. Frati, and M. R. Torrisi Up-Modulation of the Expression of Functional Keratinocyte Growth Factor Receptors Induced by High Cell Density in the Human Keratinocyte HaCaT Cell Line Cell Growth Differ., November 1, 2000; 11(11): 607 - 614. [Abstract] [Full Text]

				P. H. Michelson, M. Tigue, R. J. Panos, and P. H. S. Sporn Keratinocyte growth factor stimulates bronchial epithelial cell proliferation in vitro and in vivo Am J Physiol Lung Cell Mol Physiol, October 1, 1999; 277(4): L737 - L742. [Abstract] [Full Text] [PDF]

				C Marchese, P Mancini, F Belleudi, A Felici, R Gradini, T Sansolini, L Frati, and M. Torrisi Receptor-mediated endocytosis of keratinocyte growth factor J. Cell Sci., January 12, 1998; 111(23): 3517 - 3527. [Abstract] [PDF]

				Y. Zhang, H. Wang, S. Toratani, J. D. Sato, M. Kan, W. L. McKeehan, and T. Okamoto Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis PNAS, September 25, 2001; 98(20): 11336 - 11340. [Abstract] [Full Text] [PDF]