Sorcin (V19), a soluble acidic calcium-binding protein overproduced in multidrug-resistant cells. Identification of the protein by anti-sorcin antibody.
Sorcin (soluble resistance-related calcium-binding protein), an acidic (pI = 5.7) protein (Mr approximately 20 kDa) previously designated V19, was originally identified in cells selected for high levels of resistance to vincristine. Two-dimensional gel electrophoresis and/or Western blot techniques now show sorcin to be overproduced in cells selected for resistance to actinomycin D (QUA/ADj), colchicine (CHRC5), and adriamycin (BE(2)-C/ADR). Not all cell lines selected for resistance to these drugs overproduced sorcin; e.g. cells of an independently selected actinomycin D-resistant subline of QUA, QUA/ADsx, did not contain increased amounts of sorcin. Sorcin was purified by preparative gel electrophoresis from QUA/ADj cells and used to generate specific antiserum in chickens. By Western blot analyses the antiserum was shown to recognize sorcin in QUA/ADj and in vincristine-resistant mouse and Chinese hamster lung, colchicine-resistant Chinese hamster ovary, and adriamycin-resistant human neuroblastoma lines. Low level expression of the protein was detectable in control, drug-sensitive cells. Direct binding assays with 45Ca2+ showed that sorcin was a calcium-binding protein. QUA/ADj cells contained increased numbers of double minute chromosomes (DMs), cytogenetic indicators of gene amplification. As found for two other multidrug-resistant sublines, sorcin overproduction in QUA/ADj cells may be the result of amplification of the sorcin-encoding gene. The overproduction of this protein in multidrug-resistant cells of various species implies that sorcin plays a role in expression of the resistant phenotype.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000276:immunology; D003078:Colchicine / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D003609:Dactinomycin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005784:Gene Amplification; D006801:Humans; D007122:Immunoelectrophoresis; D008168:Lung; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000276:immunology; D009374:Neoplasms, Experimental; D009447:Neuroblastoma; D010053:Ovary; D014750:Vincristine / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; C503113:SRI protein, human; C503114:Sri protein, mouse; D003609:Dactinomycin; D014750:Vincristine; D004317:Doxorubicin; D003078:Colchicine; D002118:Calcium