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Cell Growth & Differentiation Vol. 11, 607-614, November 2000
© 2000 American Association for Cancer Research


Articles

Up-Modulation of the Expression of Functional Keratinocyte Growth Factor Receptors Induced by High Cell Density in the Human Keratinocyte HaCaT Cell Line1

Alessandro Capone2, Vincenzo Visco2, Francesca Belleudi, Cinzia Marchese, Giorgia Cardinali, Marinella Bellocci, Mauro Picardo, Luigi Frati and Maria Rosaria Torrisi3

Dipartimento di Medicina Sperimentale e Patologia, Università di Roma "La Sapienza," 00161 Roma [A. C., V. V., F. B., L. F., M. R. T.]; Istituto Nazionale Ricerca sul Cancro di Genova, Sezione di Biotecnologie, 00161 Roma [C. M.]; Istituto Dermatologico San Gallicano, 00153 Roma [G. C., M. B., M. P., M. R. T.]; and Istituto Neurologico Mediterraneo "Neuromed," 86077 Pozzilli [L. F.], Italy

Abstract

Keratinocyte growth factor (KGF) is involved in the control of proliferation and differentiation of human keratinocytes. It binds to, and activates, the tyrosine kinase KGF receptor (KGFR), a splicing transcript variant of the fibroblast growth factor receptor 2. We have previously shown (C. Marchese et al., Cell Growth Differ., 8: 989–997, 1997) that differentiation of primary cultured keratinocytes triggered by high Ca2+ concentrations in the growing medium induced up-regulation of KGFR expression, which suggested that KGFR may play a crucial role in the control of the proliferative/differentiative program during transition from basal to suprabasal cells. Here we analyzed the process of modulation of the expression of KGFRs in the human keratinocyte cell line HaCaT, widely used as a model to study keratinocyte differentiation. Western blot and double immunofluorescence for KGFR and the K1 differentiation marker showed that cell differentiation and stratification induced by confluence and high cell density correlated with an increase in KGFR expression. KGFRs, present on suprabasal differentiated cells, appeared to be efficiently tyrosine-phosphorylated by KGF, which indicated that the receptors up-regulated by differentiation can be functionally activated by ligand binding. Bromodeoxyuridine incorporation assay revealed that a significant portion of suprabasal differentiated cells expressing KGFR seemed to be still able to synthesize DNA and to proliferate in response to KGF, which suggested that increased KGFR expression may be required for retention of the proliferative activity.




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2000 by the American Association of Cancer Research.