Gene expression of TPA induced differentiation in HL-60 cells by DNA microarray analysis

Abstract

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent inducer of differentiation in human promyelocytic leukemia cells. Recently, TPA has been successfully administered to patients with myelocytic leukemia and has produced therapeutic effects that led to temporary remission. These studies demonstrated the potential efficacy of TPA in cancer chemotherapy. We now seek to understand the biological effects and molecular mechanisms of differentiation in response to TPA treatment in leukemia cells by expression profiling using DNA microarray. Our results show distinct temporal and coordinated gene changes that are consistent with differentiation and activation of multiple biochemical pathways in HL-60 cells exposed to TPA. Alterations of gene expression in HL-60 cells include various transcription factors, cytokines and protein markers that are consistent with the induction of differentiation elicited by TPA. These temporal patterns of gene expression were abolished or greatly diminished in an HL-60 derived TPA- resistant variant cell line (HL-525), thus revealing transcriptional and consequential biochemical changes that may be required for TPA-induced differentiation. In addition, certain genes were upregulated by TPA in TPA-resistant HL-525 cells but not in TPA-sensitive HL-60 cells suggesting that these genes may play a role in the resistant phenotype. These patterns of gene expression may be important for predicting response to TPA.

Development and validation of a novel reporter assay for human papillomavirus type 16 late gene expression

“…It has been demonstrated that TPA induces the expression of a number of genes that are involved in splicing in particular SC35 (serine/arginine-rich splicing factor 2) and hnRNP A2/B1 (Zheng et al, 2002). Western blot analysis confirmed an induction of hnRNP A2/B1 by TPA (Fig.…”

PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage differentiation from a monocyte

“…Expression levels of many genes change with PMA-induced differentiation of HL-60 cells, as demonstrated by using cDNA microarray analysis (29,30). Expression of cell-surface markers whose levels increase (CD11b and CD87) or decrease with differentiation (CD71) were measured by FACS to verify whether differentiation was occurring despite the loss of PDE1B2 and also to begin to characterize the phenotype of the differentiated cell.…”

Transcriptomes reflect the phenotypes of undifferentiated, granulocyte and macrophage forms of HL-60/S4 cells

“…10 The transcript level was reduced by addition of TPA. Microarray analyses of transcription in HL-60 cells examined granulocytic differentiation induced by RA 11 or DMSO, 12 macrophage differentiation induced by TPA, 13 transcript changes induced by vitamin D3 14 and a comparison of transcript level changes induced by RA or by vitamin D3. 15 More recently, transcription in HL-60 and 2 other undifferentiated myeloid leukemia cell lines, K562 and THP1, were compared by RNA-Seq and examination of enriched KEGG pathways.…”