PMID- 9332304 OWN - NLM STAT- MEDLINE DCOM- 19971119 LR - 20211203 IS - 0007-1048 (Print) IS - 0007-1048 (Linking) VI - 98 IP - 3 DP - 1997 Sep TI - Granulocyte-macrophage colony-stimulating factor abrogates transforming growth factor-beta 1-mediated cell cycle arrest by up-regulating cyclin D2/Cdk6. PG - 520-7 AB - The role of positive and negative cytokine interactions in G1 cell cycle regulation of haemopoietic cells was analysed by determination of the expression patterns of D-type cyclins and cyclin-dependent kinases (cdks) in SKM-1 myelodysplastic syndrome (MDS) cells incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or transforming growth factor-beta 1 (TGF-beta 1). TGF-beta 1 inhibited SKM-1 cell proliferation due to the cell cycle arrest in G1 phase. GM-CSF abrogated the TGF-beta 1-mediated G1 arrest in these cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TGF-beta 1-mediated G1 arrest correlated with the down-regulation of cdk4, cdk6 and cyclin D2, and that abrogation of TGF-beta 1-mediated G1 arrest by GM-CSF correlated with the constitutive over-expression of cyclin D2 and cdk6 but not cdk4. These results suggest the importance of cyclin D2/cdk6 levels in abrogating G1 arrest in cells exposed to TGF-beta 1, and raise the possibility that the GM-CSF-mediated up-regulatory pathway of signal transduction through cyclin D2/cdk6 differs from the TGF-beta 1-cdk4-mediated pathway in SKM-1 cells. This signal transduction pathway through cyclin D2/cdk6 might play an important role in haemopoietic regulation by the cytokine network. FAU - Ohtsuki, F AU - Ohtsuki F AD - Department of Paediatrics, Hyogo College of Medicine, Japan. FAU - Yamamoto, M AU - Yamamoto M FAU - Nakagawa, T AU - Nakagawa T FAU - Tanizawa, T AU - Tanizawa T FAU - Wada, H AU - Wada H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Haematol JT - British journal of haematology JID - 0372544 RN - 0 (CCND2 protein, human) RN - 0 (CCND3 protein, human) RN - 0 (Cyclin D2) RN - 0 (Cyclin D3) RN - 0 (Cyclins) RN - 0 (Transforming Growth Factor beta) RN - 136601-57-5 (Cyclin D1) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.22 (CDK6 protein, human) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 6) RN - EC 2.7.11.22 (Cyclin-Dependent Kinases) SB - IM MH - Cell Cycle/drug effects MH - Cell Division/drug effects MH - Cyclin D1/metabolism MH - Cyclin D2 MH - Cyclin D3 MH - Cyclin-Dependent Kinase 6 MH - *Cyclin-Dependent Kinases MH - Cyclins/metabolism MH - Drug Interactions MH - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology MH - Humans MH - Myelodysplastic Syndromes/pathology MH - Protein Serine-Threonine Kinases/*metabolism MH - Transforming Growth Factor beta/*pharmacology MH - Tumor Cells, Cultured MH - Up-Regulation EDAT- 1997/10/23 00:00 MHDA- 1997/10/23 00:01 CRDT- 1997/10/23 00:00 PHST- 1997/10/23 00:00 [pubmed] PHST- 1997/10/23 00:01 [medline] PHST- 1997/10/23 00:00 [entrez] AID - 10.1046/j.1365-2141.1997.2643079.x [doi] PST - ppublish SO - Br J Haematol. 1997 Sep;98(3):520-7. doi: 10.1046/j.1365-2141.1997.2643079.x.