p53/56lyn antisense shifts the 1,25-dihydroxyvitamin D3–induced G1/S block in HL60 cells to S phase

✍ Scribed by Qing Mei Wang; George P. Studzinski; Fei Chen; Frederick D. Coffman; Lawrence E. Harrison

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 288 KB
• Volume: 183
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(200005)183:2<238::aid-jcp10>3.0.co;2-1

✦ Synopsis

p53/56 lyn is a member of the src family that is predominantly expressed in hematopoietic cells and is thought to play a role in cellular proliferation. In this study, we demonstrate the participation of p53/56 lyn in 1,25-dihydroxyvitamin D 3 (1,25D 3 )-induced growth arrest in HL60 cells. We show that the mRNA and protein levels of p53/56 lyn are markedly elevated after 1,25D 3 treatment, which is accompanied by an increase of p53/56 lyn kinase activity. We also demonstrate that treatment with p53/56 lyn antisense oligodeoxynucleotides reverses the 1,25D 3 -induced G1/S block, and results in an accumulation of cells with S-phase DNA content. BrdU pulse-chase experiments reveal that this accumulation results from an increased proportion of cells actively synthesizing DNA, which are inhibited from exiting the S-phase compartment. These results indicate that upregulation of p53/56 lyn contributes significantly to the G1/S growth arrest induced by 1,25D 3 in HL60 cells and thus its activation may be a desirable outcome of chemotherapeutic regimens.