Document Detail


Activation of T-cell Protein Tyrosine Phosphatase Suppresses Keratinocyte Survival and Proliferation Following UVB Irradiation.
MedLine Citation:
PMID:  25406309     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Chronic exposure of UV radiation can contribute to the development of skin cancer by promoting PTK signaling. Studies show that exposure to UV radiation increases the ligand-independent activation of PTKs and induces PTP inactivation. In the present work, we report that TC-PTP activity is stimulated during the initial response to UVB irradiation which leads to suppression of keratinocyte cell survival and proliferation via the down-regulation of STAT3 signaling. Our results show that TC-PTP-deficient keratinocyte cell lines expressed a significantly increased level of phosphorylated STAT3 after exposure to low dose UVB. This increase corresponded with increased cell proliferation in TC-PTP-deficient keratinocytes following UVB irradiation. Loss of TC-PTP also reduced UVB-induced apoptosis. In corroboration with these results, overexpression of TC-PTP in keratinocyte cell lines yielded a decrease in phosphorylated STAT3 levels, which corresponded with a significant decrease in cell proliferation in response to low dose UVB. We demonstrate that TC-PTP activity was increased upon UVB exposure and overexpression of TC-PTP in keratinocyte cell lines further increased its activity in the presence of UVB. Treatment of TC-PTP-deficient keratinocytes with the STAT3 inhibitor STA21 significantly reduced cell viability following UVB exposure in comparison with untreated TC-PTP-deficient keratinocytes, confirming that the effect of TC-PTP on cell viability is mediated by STAT3 dephosphorylation. Combined, our results indicate that UVB-mediated activation of TC-PTP plays an important role in the STAT3-dependent regulation of keratinocyte cell proliferation and survival. Furthermore, these results suggest that TC-PTP may be a novel potential target for the prevention of UVB-induced skin cancer.
Authors:
Hyunseung Lee; Liza D Morales; Thomas J Slaga; Dae Joon Kim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-18
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-19     Completed Date:  -     Revised Date:  2014-11-20    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
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