4-Hydroxynonenal affects pRb/E2F pathway in HL-60 human leukemic cells.
4-Hydroxynonenal (HNE), a highly reactive product of lipid peroxidation, has an antiproliferative effect in several tumor cell lines and provokes alteration of cell cycle progression in HL-60 cells. HNE down-regulates c-myc expression in K562, HL-60, and MEL cells. This prompted us to study the cascade of phenomena that, starting from the CKIs expression and the phosphorylation of pRb, arrives at the E2F binding to consensus sequence in the P2 promoter of the c-myc gene. Treatment of HL-60 cells with HNE (1 microM) causes a p53-independent increase of p21(WAF1/CIP1) expression, pRb dephosphorylation, a decrease of low molecular weight E2F complexes and an increase of high molecular weight E2F complexes bound to P2 c-myc promoter. E2F4 expression is reduced by HNE treatment as well as the amount of pRb/E2F4 complexes, whereas the amount of pRb/E2F1 complexes is increased. In conclusion, HNE can affect the pRb/E2F pathway by modifying the expression of several genes involved in the control of cell proliferation.
Barrera
Giuseppina
G
Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Patologia Generale, Corso Raffaello 30, 10125 Turin, Italy.
Pizzimenti
Stefania
S
Laurora
Stefano
S
Moroni
Emanuela
E
Giglioni
Barbara
B
Dianzani
Mario U
MU
D000447:Aldehydes / Q000494:pharmacology*; D001483:Base Sequence; D018797:Cell Cycle Proteins; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050704:E2F4 Transcription Factor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016259:Genes, myc; D018922:HL-60 Cells; D006801:Humans; D010766:Phosphorylation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D000447:Aldehydes; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D004791:Enzyme Inhibitors; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases; C027576:4-hydroxy-2-nonenal