Regulation of expression of ABCB1 and LRP genes by mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and its role in generation of side population cells in canine lymphoma cell lines

Hirotaka Tomiyasu; Manabu Watanabe; Yuko Goto-Koshino; Yasuhito Fujino; Koichi Ohno; Sumio Sugano; Hajime Tsujimoto

doi:10.3109/10428194.2012.751529

Regulation of expression of ABCB1 and LRP genes by mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and its role in generation of side population cells in canine lymphoma cell lines

Hirotaka Tomiyasu, Manabu Watanabe, Yuko Goto-Koshino, Yasuhito Fujino, Koichi Ohno, Sumio Sugano, Hajime Tsujimoto

Veterinary Clinical Sciences

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

The concept of the cancer stem cell (CSC) has been recognized as key for elucidation of the mechanisms that confer the multidrug resistance (MDR) phenotype to tumor cells, and the side population (SP) fraction has been shown to be enriched by cells with the CSC phenotype. The purpose of the present study was to identify the mechanism that induces a difference of phenotype between the SP and the remaining major population (MP) using two canine lymphoma cell lines. Expression levels of ABCB1 and LRP genes, which encode efflux pumps, were significantly higher in the SP than in the MP. Microarray analysis revealed up-regulation of the expression of transforming growth factor-β (TGF-β) type II receptor in SP compared with MP, and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway was more up-regulated in the SP than in the MP. Stimulation of the MAPK/ERK pathway significantly increased the mRNA expression of both ABCB1 and LRP genes. These results indicate increased expression of the efflux pumps through the MAPK/ERK pathway in SP cells.

Original language	English (US)
Pages (from-to)	1309-1315
Number of pages	7
Journal	Leukemia and Lymphoma
Volume	54
Issue number	6
DOIs	https://doi.org/10.3109/10428194.2012.751529
State	Published - Jun 2013

Bibliographical note

Funding Information:
Th is study was supported by the Japan Society for the Promotion of Science: KAKENHI 23380182 and 24658265. We would like to thank Ms. Yumiko Ishii (IMSUT FACS Core Laboratory, Institute of Medical Science, The University of Tokyo) for operating the FACSAria and for technical advice on FACS analysis. We are indebted to Prof. Takuya Mizuno (Yamaguchi University, Japan) for providing the Ema cell line.

Keywords

ABCB1
Dog
LRP
MAPK/ERK pathway
Multidrug resistance

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Tomiyasu, H., Watanabe, M., Goto-Koshino, Y., Fujino, Y., Ohno, K., Sugano, S., & Tsujimoto, H. (2013). Regulation of expression of ABCB1 and LRP genes by mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and its role in generation of side population cells in canine lymphoma cell lines. Leukemia and Lymphoma, 54(6), 1309-1315. https://doi.org/10.3109/10428194.2012.751529

Regulation of expression of ABCB1 and LRP genes by mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and its role in generation of side population cells in canine lymphoma cell lines. / Tomiyasu, Hirotaka; Watanabe, Manabu; Goto-Koshino, Yuko et al.
In: Leukemia and Lymphoma, Vol. 54, No. 6, 06.2013, p. 1309-1315.

Research output: Contribution to journal › Article › peer-review

Tomiyasu, H, Watanabe, M, Goto-Koshino, Y, Fujino, Y, Ohno, K, Sugano, S & Tsujimoto, H 2013, 'Regulation of expression of ABCB1 and LRP genes by mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and its role in generation of side population cells in canine lymphoma cell lines', Leukemia and Lymphoma, vol. 54, no. 6, pp. 1309-1315. https://doi.org/10.3109/10428194.2012.751529

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abstract = "The concept of the cancer stem cell (CSC) has been recognized as key for elucidation of the mechanisms that confer the multidrug resistance (MDR) phenotype to tumor cells, and the side population (SP) fraction has been shown to be enriched by cells with the CSC phenotype. The purpose of the present study was to identify the mechanism that induces a difference of phenotype between the SP and the remaining major population (MP) using two canine lymphoma cell lines. Expression levels of ABCB1 and LRP genes, which encode efflux pumps, were significantly higher in the SP than in the MP. Microarray analysis revealed up-regulation of the expression of transforming growth factor-β (TGF-β) type II receptor in SP compared with MP, and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway was more up-regulated in the SP than in the MP. Stimulation of the MAPK/ERK pathway significantly increased the mRNA expression of both ABCB1 and LRP genes. These results indicate increased expression of the efflux pumps through the MAPK/ERK pathway in SP cells.",

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N2 - The concept of the cancer stem cell (CSC) has been recognized as key for elucidation of the mechanisms that confer the multidrug resistance (MDR) phenotype to tumor cells, and the side population (SP) fraction has been shown to be enriched by cells with the CSC phenotype. The purpose of the present study was to identify the mechanism that induces a difference of phenotype between the SP and the remaining major population (MP) using two canine lymphoma cell lines. Expression levels of ABCB1 and LRP genes, which encode efflux pumps, were significantly higher in the SP than in the MP. Microarray analysis revealed up-regulation of the expression of transforming growth factor-β (TGF-β) type II receptor in SP compared with MP, and the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway was more up-regulated in the SP than in the MP. Stimulation of the MAPK/ERK pathway significantly increased the mRNA expression of both ABCB1 and LRP genes. These results indicate increased expression of the efflux pumps through the MAPK/ERK pathway in SP cells.

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Regulation of expression of ABCB1 and LRP genes by mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and its role in generation of side population cells in canine lymphoma cell lines

Abstract

Bibliographical note

Keywords

UN SDGs

Access

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