Nuclear chromatin patterns in 3 glucocorticoid-resistant RPMI 8226 human myeloma cell sub-lines: correlations with cell growth and immunological phenotype.
Nuclear morphological alterations associated with glucocorticoid resistance in human myeloma were evaluated by image cytometry in three human myeloma RPMI 8226 cell sub-lines. Resistance was induced by drug selection using prednisone (8226p), methylprednisolone (8226m) and dexamethasone (8226d), respectively. All these three cell sub lines displayed significant glucocorticoid-resistance without cross-resistance to doxorubicin. Nuclear geometry and texture were analyzed on G0/G1-selected cell nuclei and data compared with cell growth characteristics and membrane expression of CD23, CD38, CD44 and CD58 antigens. When compared to the parental RPMI 8226 cell line, glucocorticoid-resistant cells display a progressive chromatin condensation with heterogeneously distributed large chromatin clumps, a phenomenon not observed in the multidrug-resistant CEM-VLB cells. These alterations were correlated to the resistance index against glucocorticoids and to the expressions of CD38, and of CD44 variant forms CD44v5 and CD44v7-8 antigens. These data suggest that glucocorticoid resistance in RPMI 8226 cells could be associated with sub-visual specific higher-order chromatin organization changes. Furthermore, these alterations are correlated to the expression of membrane markers associated with tumors aggressiveness.
Genty
Vincent
V
Institut Biotechnologique de Troyes, France.
El-Khoury
Victoria
V
Liautaud-Roger
Françoise
F
Dine
Gérard
G
Dufer
Jean
J
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure*; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure*; D003907:Dexamethasone / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D008775:Methylprednisolone / Q000494:pharmacology; D009101:Multiple Myeloma / Q000276:immunology / Q000648:ultrastructure*; D010641:Phenotype; D011241:Prednisone / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D002843:Chromatin; D005938:Glucocorticoids; D018960:Hyaluronan Receptors; D003907:Dexamethasone; D004317:Doxorubicin; D051997:ADP-ribosyl Cyclase 1; D011241:Prednisone; D008775:Methylprednisolone