title: 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.
authors.affiliation: Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
authors.forename: Roald
authors.initials: R
authors.lastname: Ravatn
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Wei-Chung
authors.initials: WC
authors.lastname: Shih
authors.forename: Arnold
authors.initials: A
authors.lastname: Rabson
authors.forename: Roger
authors.initials: R
authors.lastname: Strair
authors.forename: Eliezer
authors.initials: E
authors.lastname: Huberman
authors.forename: Allan
authors.initials: A
authors.lastname: Conney
authors.forename: Khew-Voon
authors.initials: KV
authors.lastname: Chin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012334:RNA, Neoplasm; D013755:Tetradecanoylphorbol Acetate