Comparative effects of microtubules disruption on glucocorticoid receptor functions in proliferating and quiescent cells.
We have recently demonstrated that the alkaloid colchicine (COL) inhibits glucocorticoid receptor (GR) transcriptional activity. In addition, we described proteasome-mediated degradation of GR in COL-treated HeLa cells. While these effects were previously attributed to cell cycle arrest in G2/M phase, this explanation is not applicable for nonproliferating cells such as human hepatocytes (HH). In the current study, we compared COL-mediated microtubule disruption and cell cycle arrest with selected GR functions in HeLa cells and HH as models of proliferating and quiescent cells, respectively. Microtubule disruption led to irreversible decrease in GR binding capacity and protein level in HeLa cells. None of the parameters was restored 24 hours after COL withdrawal. In contrast, dexamethasone (DEX) binding was increased in HH at the beginning of the treatment, with following transient activation of extracellular signal-regulated kinase (ERK). The findings of these investigations emphasize the GR-signaling differences between primary and transformed cells.
Vrzal
Radim
R
Department of Cell Biology and Genetics, Faculty of Science, Palacký University Olomouc, Slechtitelů 11, Olomouc, Czech Republic. radim.vrzal@email.cz
Gerbal-Chaloin
Sabine
S
Maurel
Patrick
P
Dvorák
Zdenĕk
Z
D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003078:Colchicine / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006367:HeLa Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008024:Ligands; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects* / Q000648:ultrastructure; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology*
D008024:Ligands; D011965:Receptors, Glucocorticoid; D050257:Tubulin Modulators; C028697:dexamethasone receptor; D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D003078:Colchicine