GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma
Side population (SP) cells are an enriched population of stem, and the existence of SP cells has been reported in human cancer cell lines. In this study, we performed an SP analysis using 11 human cancer cell lines and confirmed the presence of SP cells in an embryonic carcinoma cell line, NEC8. NEC...
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doaj-5ca7d53499104ef6bca59503afecc9dd2020-11-24T23:05:05ZengHindawi LimitedStem Cells International1687-96782010-01-01201010.4061/2010/782967782967GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic CarcinomaToshihiko Inowa0Keiichi Hishikawa1Yumi Matsuzaki2Takayuki Isagawa3Takumi Takeuchi4Hiroyuki Aburatani5Tadaichi Kitamura6Toshiro Fujita7Department of Urology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, JapanDepartment of Clinical Renal Regeneration, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, JapanDepartment of Physiology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo, 160-8582, JapanGenome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, JapanDepartment of Urology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, JapanGenome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, JapanDepartment of Urology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, JapanDepartment of Clinical Renal Regeneration, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, JapanSide population (SP) cells are an enriched population of stem, and the existence of SP cells has been reported in human cancer cell lines. In this study, we performed an SP analysis using 11 human cancer cell lines and confirmed the presence of SP cells in an embryonic carcinoma cell line, NEC8. NEC8 SP cells showed characteristics of cancer stem cells, such as high growth rate, chemoresistance and high invasiveness. To further characterize the NEC8 SP cells, we used DNA microarrays. Among 38,500 genes, we identified 12 genes that were over-expressed in SP cells and 1 gene that was over-expressed in non-SP cells. Among these 13 genes, we focused on GADD45b. GADD45b was over-expressed in non-SP cells, but the inhibition of GADD45b had no effect on non-SP cells. Paradoxically, the inhibition of GADD45b significantly reduced the viability of NEC8 SP cells. The inhibition of ABCG2, which determines the SP phenotype, had no effect on the invasiveness of NEC8 SP cells, but the inhibition of GADD45b significantly reduced invasiveness. These results suggest that GADD45b, but not ABCG2, might determine the cancer stem cell-like phenotype, such as chemoresistance and the high invasiveness of NEC8 SP cells, and might be a good therapeutic target.http://dx.doi.org/10.4061/2010/782967 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Toshihiko Inowa Keiichi Hishikawa Yumi Matsuzaki Takayuki Isagawa Takumi Takeuchi Hiroyuki Aburatani Tadaichi Kitamura Toshiro Fujita |
spellingShingle |
Toshihiko Inowa Keiichi Hishikawa Yumi Matsuzaki Takayuki Isagawa Takumi Takeuchi Hiroyuki Aburatani Tadaichi Kitamura Toshiro Fujita GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma Stem Cells International |
author_facet |
Toshihiko Inowa Keiichi Hishikawa Yumi Matsuzaki Takayuki Isagawa Takumi Takeuchi Hiroyuki Aburatani Tadaichi Kitamura Toshiro Fujita |
author_sort |
Toshihiko Inowa |
title |
GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma |
title_short |
GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma |
title_full |
GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma |
title_fullStr |
GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma |
title_full_unstemmed |
GADD45β Determines Chemoresistance and Invasive Growth of Side Population Cells of Human Embryonic Carcinoma |
title_sort |
gadd45β determines chemoresistance and invasive growth of side population cells of human embryonic carcinoma |
publisher |
Hindawi Limited |
series |
Stem Cells International |
issn |
1687-9678 |
publishDate |
2010-01-01 |
description |
Side population (SP) cells are an enriched population of stem, and the existence of SP cells has been reported in human cancer cell lines. In this study, we performed an SP analysis using 11 human cancer cell lines and confirmed the presence of SP cells in an embryonic carcinoma cell line, NEC8. NEC8 SP cells showed characteristics of cancer stem cells, such as high growth rate, chemoresistance and high invasiveness. To further characterize the NEC8 SP cells, we used DNA microarrays. Among 38,500 genes, we identified 12 genes that were over-expressed in SP cells and 1 gene that was over-expressed in non-SP cells. Among these 13 genes, we focused on GADD45b. GADD45b was over-expressed in non-SP cells, but the inhibition of GADD45b had no effect on non-SP cells. Paradoxically, the inhibition of GADD45b significantly reduced the viability of NEC8 SP cells. The inhibition of ABCG2, which determines the SP phenotype, had no effect on the invasiveness of NEC8 SP cells, but the inhibition of GADD45b significantly reduced invasiveness. These results suggest that GADD45b, but not ABCG2, might determine the cancer stem cell-like phenotype, such as chemoresistance and the high invasiveness of NEC8 SP cells, and might be a good therapeutic target. |
url |
http://dx.doi.org/10.4061/2010/782967 |
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