| The protease inhibitor, elafin, induces p53-dependent apoptosis in human melanoma cells. | |
| | |
MedLine Citation:
|
PMID: 20020498 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Expression of the protease inhibitor elafin is deregulated in several human cancers. However, functions of the protein in cancer are yet to be established. Here, we show that elafin elicits pro-apoptotic effects in melanoma cells but not in normal melanocytes. Elafin triggered the intrinsic apoptotic pathway as evidenced by the increased caspase 9 activity and unaltered caspase 8 activity. Caspase 9-specific siRNA, but not caspase 8-specific siRNA, dramatically abrogated elafin-induced apoptosis. Elevated level of p53 was observed, resulting in increased transcriptional activation and consequent expression of downstream effector molecules (Bax, Puma, Noxa, p21). Moreover, the apoptotic effect of elafin was inhibited by p53-specific siRNA and the p53 inhibitor pifithrin-alpha. Elafin treatment of xenograft mice of melanoma cells led to significantly smaller tumor sizes compared with those of untreated control mice. Immunohistochemical analysis revealed decreased elafin expression in melanoma tissue specimens. Western blot and reverse transcription analyses indicated transcriptional repression of the elafin gene in melanoma cells. Our results collectively indicate that elafin induces apoptosis in melanoma cells through a p53-dependent intrinsic apoptotic pathway, and that repression of elafin expression in melanoma may contribute to disease progression. |
| | |
Authors:
|
Kyung Sook Yu; Yangsoon Lee; Chung Mi Kim; Eui-Chul Park; Juhyun Choi; Dae-Sik Lim; Young-Hwa Chung; Sang Seok Koh |
Related Documents
:
|
18793918 - Mechanisms of n-acetyl cysteine-mediated protection from 2-hydroxyethyl methacrylate-in... 19733388 - Propolis from turkey induces apoptosis through activating caspases in human breast carc... 19519938 - Letting go: modification of cell adhesion during apoptosis. 18684108 - Apoptotic sensitivity of murine iap-deficient cells. 18793918 - Mechanisms of n-acetyl cysteine-mediated protection from 2-hydroxyethyl methacrylate-in... 21252908 - F-box protein 10, an nf-κb-dependent anti-apoptotic protein, regulates trail-induced a... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: International journal of cancer. Journal international du cancer Volume: 127 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2010 Sep |
Date Detail:
|
Created Date: 2010-07-27 Completed Date: 2010-08-24 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
|
Languages: eng Pagination: 1308-20 Citation Subset: IM |
Affiliation:
|
Therapeutic Antibody Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis / drug effects*, physiology Blotting, Western Cell Line, Tumor Cell Proliferation Down-Regulation Elafin / pharmacology* Humans Immunohistochemistry Melanoma / metabolism, pathology* Mice Mice, Nude Neoplasm Transplantation Protease Inhibitors / pharmacology* RNA, Small Interfering Recombinant Proteins / pharmacology Reverse Transcriptase Polymerase Chain Reaction Tumor Suppressor Protein p53 / physiology* |
| Chemical | |
Reg. No./Substance:
|
0/Elafin; 0/Protease Inhibitors; 0/RNA, Small Interfering; 0/Recombinant Proteins; 0/Tumor Suppressor Protein p53 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: miR-212 is down-regulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer.
Next Document: Toward a population genetic framework of developmental evolution: the costs, limits, and consequence...