title: The regulation of the expression of ABCG2 gene through mitogen-activated protein kinase pathways in canine lymphoid tumor cell lines.
abstract: Treatments for canine lymphoma often fail, because tumor cells acquire multidrug resistance (MDR). MDR can develop through several mechanisms, among which the overexpression of drug transporters in tumor cells is a well-studied mechanism. ATP-binding cassette sub-family G member 2 (ABCG2) belongs to the ABC-transporters, that are representative drug efflux pumps associated with MDR in human tumor cells. However, the regulation of ABCG2 gene expression in canine tumors is not well understood. The purpose of the present study was to reveal the regulatory mechanism of ABCG2 gene expression in 4 canine lymphoid tumor cell lines, GL-1, CLBL-1, UL-1 and Ema. Treatment with phorbol 12-myristate 13-acetate (PMA), the protein kinase C (PKC) activator, stimulated MAPK/ERK pathway in GL-1, UL-1 and Ema cells and JNK pathway in UL-1 and Ema cells. When GL-1 and UL-1 cells were treated with PMA and the MAPK/ERK kinase inhibitor U0126, ABCG2 gene expression levels were elevated above those in untreated cells. Similarly, ABCG2 gene expression increased above control levels in UL-1 and Ema cells treated with PMA and the JNK inhibitor SP600125. However, ABCG2 gene expression was unaffected by U0126 exposure in CLBL-1 cells, in which activation of MAPK/ERK pathway was observed in non-treated cells. These results suggested that MAPK/ERK and JNK pathways downregulate ABCG2 gene expression, which is upregulated by unidentified but possibly PKC-dependent pathways, in several types of canine lymphoid tumor cells.
authors.affiliation: Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tomiyasu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Goto-Koshino
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Fujino
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohno
authors.forename: Hajime
authors.initials: H
authors.lastname: Tsujimoto
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes; D045744:Cell Line, Tumor; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric
chemical_list: D018528:ATP-Binding Cassette Transporters; D000873:Anthracenes; C432165:pyrazolanthrone; D020928:Mitogen-Activated Protein Kinases