Premium
Reduction of cell cycle progression in human erythroid progenitor cells treated with tumour necrosis factor alpha occurs with reduced CDK6 and is partially reversed by CDK6 transduction
Author(s) -
Dai Chunhua,
Chung IkJoo,
Jiang Shazi,
Price James O.,
Krantz Sanford B.
Publication year - 2003
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.1365-2141.2003.04367.x
Subject(s) - cyclin dependent kinase 6 , cell cycle , tumor necrosis factor alpha , biology , apoptosis , cell growth , microbiology and biotechnology , cyclin d1 , cancer research , endocrinology , biochemistry
Summary. Tumor necrosis factor α (TNFα) potently inhibits the in vitro growth of highly purified human d‐6 erythroid colony forming cells (ECFC). Unlike the inhibitory effect of TNFα on other cells, including more immature ECFC, this antiproliferative effect of TNFα is not related to apoptosis because the d‐6 cell descendants were morphologically normal, without apoptosis by terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labelling assay and without caspase activation by Western blots after TNFα treatment. TNFα did not appear to affect the cell cycle distribution, but the cell cycle duration was significantly longer in TNFα‐treated cells. DNA synthesis was also significantly reduced by TNFα. Studies of various proteins that regulate the cell cycle showed that cyclin‐dependent kinase 6 (CDK6) protein and mRNA levels were concomitantly decreased in the presence of TNFα, suggesting that inhibition of cell growth was related to reduced CDK6. To evaluate this, the CDK6 gene was transferred into ECFC using green fluorescence protein‐retrovirus‐mediated gene transfer. The results showed that the level of cell growth produced by TNFα was increased by 30% when the cells were transfected with CDK6 . Therefore, the modification of cell cycle progression in the presence of TNFα through a reduction of CDK6 is an important mechanism in the TNFα inhibition of human ECFC expansion.