Glucocorticoid inhibition of 235-1 rat pituitary tumor cell cycle progression.
Control of the cell cycle is accomplished by sequentially activated cyclin-dependent kinases and the action of inhibitory proteins. We have shown that exposure of 235-1 rat pituitary tumor cells to dexamethasone (DEX) leads to a 50% reduction in growth rate. We examined the mechanism by which DEX affects 235-1 cell proliferation by determining the expression levels of proteins involved in cell-cycle progression. The expression of the G1 markers c-Myc and cyclin D3 were unaffected by DEX treatment. Levels of retinoblastoma family proteins p107 and p116 Rb were not altered. The levels of p1 30/Rb2 were increased by DEX within 36 h of initiating treatment. Additionally, a higher-mobility Rb2-related protein appeared within 24 h and was further increased in DEX-treated cells by 36 h. We also observed reduced levels of M-phase proteins, Cdc2 kinase, and cyclin B in DEX-treated cells. These changes occurred prior to the reduction in cell numbers and thus may represent causative factors. Our data suggest that DEX induces a late G1 block in 235-1 cell-cycle passage, accompanied by a reduction in the levels of the regulatory proteins required for passage through subsequent phases of the cell cycle.
Delidow
Beverly C
BC
Department of Biochemistry and Molecular Biology, Marshall University School of Medicine, Huntington, WV 25704, USA. delidow@marshall.edu
Wang
Miranda
M
Bhamidipaty
Sonita V
SV
Black
Lynn D
LD
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D056743:Cyclin D3; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015175:Prolactinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D051381:Rats; D016160:Retinoblastoma Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism
C534701:Ccnb1 protein, rat; C534698:Ccnd3 protein, rat; C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D056743:Cyclin D3; D016213:Cyclins; D005938:Glucocorticoids; D016271:Proto-Oncogene Proteins c-myc; D012334:RNA, Neoplasm; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003907:Dexamethasone; D016203:CDC2 Protein Kinase