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Gene Expression Profile of Colon Cancer Cell Lines Treated with SN-38

Wallin, A.; Francis, Princy LU ; Nilbert, Mef LU ; Svanvik, J. and Sun, X. -F. (2010) In Chemotherapy 56(1). p.17-25
Abstract
Aim: Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis. Material and Methods: The study included 3 colon cancer cell lines: KM12C, KM12SM... (More)
Aim: Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis. Material and Methods: The study included 3 colon cancer cell lines: KM12C, KM12SM and KM12l4a. The 3 cell lines were treated with SN-38, and samples were obtained after 24 and 48 hour treatments. The gene expression analyses were performed using oligonucleotide microarrays comprising of similar to 27,000 spots where the untreated controls were compared to the SN-38-treated samples. Results: Unsupervised clustering clearly distinguished the treated cell lines from the untreated. Supervised analysis identified 3,974 significant genes (p = 0.05) differentiating the treated samples from the untreated, majority of which were down-regulated after treatment. The top-ranked down-regulated genes in the treated cell lines included those related to receptor and kinase activity, signal transduction, apoptosis, RNA processing, protein metabolism and transport, cell cycle and transcription. A smaller number of genes were up-regulated in the cell lines after treatment and included genes involved in apoptosis, transcription, development and differentiation. Conclusions: These results demonstrate that the expression of the genes involved in cell proliferation and apoptosis as well as RNA, DNA and protein metabolism were affected by SN-38. The impact of certain genes on colorectal cancer development needs to be further evaluated; however, these results could serve as a basis for further studies in order to find targets for irinotecan treatment. Copyright (C) 2010 S. Karger AG, Basel (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
KM12C, KM12L4a, Colorectal cancer, Gene expression, KM12SM, SN-38
in
Chemotherapy
volume
56
issue
1
pages
17 - 25
publisher
Karger
external identifiers
  • wos:000276593500003
  • scopus:77950541479
ISSN
0009-3157
DOI
10.1159/000287353
language
English
LU publication?
yes
id
c2326d40-d612-46b0-9caa-5cf212ccc892 (old id 1603950)
date added to LUP
2010-05-19 08:09:14
date last changed
2018-05-29 09:29:56
@article{c2326d40-d612-46b0-9caa-5cf212ccc892,
  abstract     = {Aim: Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis. Material and Methods: The study included 3 colon cancer cell lines: KM12C, KM12SM and KM12l4a. The 3 cell lines were treated with SN-38, and samples were obtained after 24 and 48 hour treatments. The gene expression analyses were performed using oligonucleotide microarrays comprising of similar to 27,000 spots where the untreated controls were compared to the SN-38-treated samples. Results: Unsupervised clustering clearly distinguished the treated cell lines from the untreated. Supervised analysis identified 3,974 significant genes (p = 0.05) differentiating the treated samples from the untreated, majority of which were down-regulated after treatment. The top-ranked down-regulated genes in the treated cell lines included those related to receptor and kinase activity, signal transduction, apoptosis, RNA processing, protein metabolism and transport, cell cycle and transcription. A smaller number of genes were up-regulated in the cell lines after treatment and included genes involved in apoptosis, transcription, development and differentiation. Conclusions: These results demonstrate that the expression of the genes involved in cell proliferation and apoptosis as well as RNA, DNA and protein metabolism were affected by SN-38. The impact of certain genes on colorectal cancer development needs to be further evaluated; however, these results could serve as a basis for further studies in order to find targets for irinotecan treatment. Copyright (C) 2010 S. Karger AG, Basel},
  author       = {Wallin, A. and Francis, Princy and Nilbert, Mef and Svanvik, J. and Sun, X. -F.},
  issn         = {0009-3157},
  keyword      = {KM12C,KM12L4a,Colorectal cancer,Gene expression,KM12SM,SN-38},
  language     = {eng},
  number       = {1},
  pages        = {17--25},
  publisher    = {Karger},
  series       = {Chemotherapy},
  title        = {Gene Expression Profile of Colon Cancer Cell Lines Treated with SN-38},
  url          = {http://dx.doi.org/10.1159/000287353},
  volume       = {56},
  year         = {2010},
}