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Granulocyte‐macrophage colony‐stimulating factor abrogates transforming growth factor‐β1‐mediated cell cycle arrest by up‐regulating cyclin D2/Cdk6
Author(s) -
Ohtsuki Fumiko,
Yamamoto Masuji,
Nakagawa Toshitaro,
Tanizawa Takakuni,
Wada Hiroyoshi
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.2643079.x
Subject(s) - cyclin d , cyclin dependent kinase 6 , cyclin dependent kinase , cyclin d3 , cyclin a , microbiology and biotechnology , cell cycle , cyclin d2 , cyclin a2 , cell cycle checkpoint , biology , signal transduction , cancer research , cyclin , transforming growth factor , cyclin e , cell , biochemistry
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‐β1 (TGF‐β1). TGF‐β1 inhibited SKM‐1 cell proliferation due to the cell cycle arrest in G1 phase. GM‐C18SF abrogated the TGF‐β1‐mediated G1 arrest in these cells. Reverse transcription‐polymerase chain reaction (RT‐PCR) analysis indicated that TGF‐β1‐mediated G1 arrest correlated with the down‐regulation of cdk4, cdk6 and cyclin D2, and that abrogation of TGF‐β1‐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‐β1, and raise the possibility that the GM‐CSF‐mediated up‐regulatory pathway of signal transduction through cyclin D2/cdk6 differ s from the TGF‐β1‐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.