| Novel variants of muscle calpain 3 identified in human melanoma cells: cisplatin-induced changes in vitro and differential expression in melanocytic lesions. | |
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MedLine Citation:
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PMID: 19386580 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Calpains are cysteine proteases comprising members ubiquitously expressed in human tissues and other tissue-specific isoforms. Alterations of calpain 3 (p94), the muscle-specific isoform that contains three peculiar sequences (NS, IS1 and IS2), are strictly associated to the limb-girdle muscular dystrophy type 2A, in which a myonuclear apoptosis has been documented. Our recent demonstration of a proapoptotic role of ubiquitous calpains in drug-induced apoptosis of melanoma cells prompted us to investigate the expression of calpain 3 in human melanoma cell lines undergoing apoptosis and in melanocytic lesions. In melanoma cell lines, we have identified two novel splicing variants of calpain 3 (hMp78 and hMp84): they have an atypical initiation exon and a putative nuclear localization signal, the shorter one lacks IS1 inset and both proteins are extremely unstable. Virtually, both isoforms (prevalently as cleavage forms) are localized in cytoplasm and in nucleoli. In cisplatin-treated preapoptotic cells, an increase of both transcription and autoproteolytic cleavage of the novel variants is observed; the latter event is prevented by the inhibitor of ubiquitous calpains, calpeptin, which is also able to protect from apoptosis. Interestingly, among melanocytic lesions, the expression of these novel variants is significantly downregulated, compared with benign nevi, in the most aggressive ones, i.e. in vertical growth phase melanoma and, even more, in metastatic melanoma cells, characterized by invasiveness properties and usually highly resistant to apoptosis. On the whole, our observations suggest that calpain 3 variants can play a proapoptotic role in melanoma cells and its downregulation, as observed in highly aggressive lesions, could contribute to melanoma progression. |
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Authors:
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D Moretti; B Del Bello; E Cosci; M Biagioli; C Miracco; E Maellaro |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-21 |
Journal Detail:
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Title: Carcinogenesis Volume: 30 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-04 Completed Date: 2009-06-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 960-7 Citation Subset: IM |
Affiliation:
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Department of Physiopathology, Experimental Medicine and Public Health, University of Siena, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alternative Splicing Antineoplastic Agents / pharmacology* Apoptosis Biopsy Calpain / antagonists & inhibitors, metabolism* Cell Line, Tumor Cell Nucleolus / metabolism Cisplatin / pharmacology* Cytoplasm / metabolism Dipeptides / pharmacology Dysplastic Nevus Syndrome / metabolism Gene Expression Regulation, Neoplastic Humans Melanoma / metabolism*, pathology Muscle Proteins / antagonists & inhibitors, metabolism* Neoplasm Metastasis Nevus / metabolism* RNA, Messenger / metabolism Skin Neoplasms / metabolism*, pathology |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Dipeptides; 0/Muscle Proteins; 0/RNA, Messenger; 117591-20-5/calpeptin; 15663-27-1/Cisplatin; EC 3.4.22.-/CAPN3 protein, human; EC 3.4.22.-/Calpain |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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