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Molecular mechanisms of different sensitivity of tumor cells to dexamethasone
A S Dukhanin1, E A Romanova, E A Dukhanina
1Russian State Medical University, Moscow. buh@genome.eimb.relarn.ru
Abstract:
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.
Insights
Metastasin expression confers resistance to dexamethasone-induced apoptosis in CSML-100 cells. This resistance is linked to metastasin
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Glucocorticoids, like dexamethasone, induce apoptosis in cancer cells.
- Metastasin, an S-100 family protein, is implicated in cell behavior.
- Differential expression of metastasin in cell lines CSML-0 and CSML-100 was observed.
Purpose of the Study:
- To investigate the role of metastasin in cellular response to dexamethasone.
- To elucidate the mechanisms underlying dexamethasone resistance in CSML-100 cells.
Main Methods:
- Cell culture of CSML-0 and CSML-100 cell lines.
- Treatment with dexamethasone, Ca-ATPase inhibitors (vanadate, thapsigargin).
- Assay of Ca-ATPase activity and ATP-dependent Ca2+ transport in plasmolemmal fractions.
Main Results:
- Dexamethasone induced apoptosis in CSML-0 cells (metastasin-negative).
- CSML-100 cells (metastasin-high) were resistant to dexamethasone-induced apoptosis.
- Metastasin activated Ca-ATPase and ATP-dependent Ca2+ transport.
- Inhibition of Ca-ATPase sensitized CSML-100 cells to dexamethasone.
Conclusions:
- Metastasin expression confers resistance to dexamethasone-induced apoptosis.
- Metastasin-mediated activation of Ca-ATPase is a key mechanism for this resistance.
- Targeting Ca-ATPase may overcome dexamethasone resistance in metastasin-expressing cancers.