Molecular mechanisms of different sensitivity of tumor cells to dexamethasone.
The response of two cell lines, CSML-0 (does not express metastasin) and CSML-100 (high expression of metastasin) to cytolytic action of glucocorticoid was studied. Dexamethasone (1 microM) induced apoptosis of CSML-0 cells, while CSLM-100 cells were resistant to its cytolytic action. Apoptotic death of CSLM-100 cells was induced by incubation with dexamethasone in the presence of Ca-ATPase inhibitors, vanadate or thapsigargin. Metastasin, a proteins of the S-100 family, activated Ca-ATPase and ATP-dependent Ca2+ transport in plasmolemmal fraction of CSML-100 cells. Experiments showed that metastasin-induced activation of Ca-ATPase is a possible mechanisms of CSML-100 cell resistance to cytolytic dexamethasone action.
Dukhanin
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Russian State Medical University, Moscow. buh@genome.eimb.relarn.ru
Romanova
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EA
Dukhanina
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EA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004586:Electrophoresis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism* / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D014638:Vanadates; D019284:Thapsigargin; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium