Abstract
Keratinocyte growth factor (KGF) is a potent and specific mitogen for different types of epithelial cells, including keratinocytes of the skin. To gain insight into the mechanisms of KGF action in this tissue, we attempted to identify genes that are regulated by KGF in keratinocytes. Using the differential display reverse transcription polymerase chain reaction technology, a gene was identified which was strongly induced in these cells by treatment with KGF but not with serum growth factors or pro-inflammatory cytokines. This gene seems to be part of a multigene family as assessed by Southern blot analysis. Molecular cloning and sequencing of the full-length cDNA revealed a strong homology with the yeast CHL1 gene. The latter encodes a putative helicase, which is involved in correct chromosome transmission and cell cycle progression. Furthermore, the CHL1 gene product and the protein encoded by the novel KGF-regulated gene were identical in size, indicating that we had cloned the human CHL1 homologue. This finding suggests a novel and specific role of KGF in correct chromosome segregation and/or cell cycle progression.
Highlights
Keratinocyte growth factor (KGF)1 is a member of the fibroblast growth factor (FGF) family of mitogens that acts on epithelial cells, including keratinocytes of the skin [1, 2]
Identification of a KGF-regulated Gene by DDRT-PCR—To elucidate the mechanisms of KGF action in keratinocytes, we attempted to identify genes that are regulated by this growth factor in keratinocytes
The HaCaT keratinocyte cell line, which is known to express functional KGF receptors,3 was used for these studies
Summary
Keratinocyte growth factor (KGF)1 is a member of the fibroblast growth factor (FGF) family of mitogens that acts on epithelial cells, including keratinocytes of the skin [1, 2]. The novel cDNA revealed a striking homology to the yeast CHL-1 gene that encodes a putative helicase involved in chromosome transmission and normal cell cycle progression. This fragment had been obtained by DDRT-PCR (ii); 275-base pair probe corresponding to amino acids 664 –756 of the KRG-2 open reading frame.
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