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Changes in glucocorticoid-induced apoptosis and in expression of Bcl-2 protein during long-term culture of thymic lymphoma

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Kobzdej M., Matuszyk J., Ziolo E., Strzada?a L., Strzada?a L.

Archivum Immunologiae et Therapiae Experimentalis

2000

vol. 48

issue 1

43-46

Lymphomagenesis is a multistep process progressively freeing transformed thymocytes from external regulatory signals, i. e. thymic developmental program controlling growth, differentiation or apoptosis. Here we report that cells of thymic lymphoma overexpressing Ras/Raf proteins, initially resistant to TCR-dependent apoptosis but sensitive to dexamethasone- and etoposide-induced cell death, became insensitive to dexamethasone after long-time culture. That transition correlated with a strong increase in the expression of the anti-apoptotic Bcl-2 protein. Interestingly, lymphoma cells were still sensitive to p53-mediated apoptosis induced by etoposide. It suggests that the anti-apoptotic activity of Bcl-2 is correlated with a resistance to glucocorticoid-induced apoptosis but not to p53-mediated apoptosis. The sequence of mutations in the process of lymphomagenesis seems to be composed of at least 3 main hits which equip the cells with independence from external mitogenic signals (activation of Ras/Raf), resistance to inducers of apoptosis (activation of Bcl-2) and generation of cellular heterogeneity (deletion of p53) important in tumor progression.

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1 Archivum Immunologiae et Therapiae Experimentalis

1 2000

1 Kobzdej M.

1 Matuszyk J.

1 Strzada?a L.

1 Ziolo E.

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Changes in glucocorticoid-induced apoptosis and in expression of Bcl-2 protein during long-term culture of thymic lymphoma