Regulation of guanylate-binding protein expression in interferon-y treated human epidermal keratinocytes and squamous cell carcinoma cells

Saunders, Nicholas A., Smith, Robert and Jettens, Anton (1999) Regulation of guanylate-binding protein expression in interferon-y treated human epidermal keratinocytes and squamous cell carcinoma cells. Journal of Investigative Dermatology, 112 6: 977-983. doi:10.1046/j.1523-1747.1999.00611.x


Author Saunders, Nicholas A.
Smith, Robert
Jettens, Anton
Title Regulation of guanylate-binding protein expression in interferon-y treated human epidermal keratinocytes and squamous cell carcinoma cells
Journal name Journal of Investigative Dermatology   Check publisher's open access policy
ISSN 0022-202X
1523-1747
Publication date 1999-01-01
Sub-type Article (original research)
DOI 10.1046/j.1523-1747.1999.00611.x
Open Access Status
Volume 112
Issue 6
Start page 977
End page 983
Total pages 7
Place of publication London, United Kingdom
Publisher Nature
Language eng
Formatted abstract
Interferon-γ is a potent inducer of growth arrest and squamous differentiation of human epidermal keratinocytes in vitro. In order to understand the proximate events regulating interferon-γ action we studied the relationship between interferon-γ-mediated induction of a cytoplasmic guanylate-binding protein and the expression of growth and differentiation marker genes in normal and transformed keratinocytes. Induction of guanylate- binding protein mRNA by interferon-γ was detectable at 4 h, was transcription dependent, and preceded changes in the expression of markers of growth arrest (E2F-1 mRNA downregulation) and differentiation (SQ37 mRNA induction). The Ec 50 value for guanylate-binding protein induction (4 units interferon-γ per ml) was lower than previously reported for SQ37 (40 units interferon-γ per ml). Guanylate-binding protein mRNA appeared to be only moderately downregulated by modulators of the squamous phenotype such as retinoic acid and transforming growth factor-β1. In addition, mRNA levels of E2F-1 or SQ37 were not altered in several squamous carcinoma cell lines treated with interferon-γ. In contrast, guanylate-binding protein mRNA was highly induced in all these cell lines following interferon-γ treatment. Further analysis of the signal transduction pathway mediating interferon-γ responses using protein kinase inhibitors indicated that guanylate-binding protein induction in normal human epidermal keratinocyte cells was most likely protein kinase C independent. Our data suggest that more than one postreceptor interferon-γ signaling pathway exists in keratinocytes and that at least one of these pathways is defective in squamous carcinoma cells. Furthermore, our data demonstrated that the failure of the squamous carcinoma cells to undergo interferon-γ-induced growth arrest and differentiation is not due to an inherent defect in interferon-γ receptor activation, but most likely is due to a defect in a non-guanylate-binding protein-dependent signaling pathway.
Keyword Cancer
Epithelium
Squamous differentiation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Diamantina Institute - Open Access Collection
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 11 Jun 2008, 01:28:30 EST