Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition

Bostjan Humar1, Les McNoe1, Anita Dunbier1, Rosemary Heathcott1, Antony W Braithwaite2, Anthony E Reeve11Cancer Genetics Laboratory, Department of Biochemistry; University of Otago, Dunedin, Aotearoa New Zealand; 2Children&#39;s Medical Research Institute, Wintworthbill, NSW, AustraliaAbstra...

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Autores principales:	Bostjan Humar, Les McNoe, Anita Dunbier, Rosemary Heathcott, Antony W Braithwaite, Anthony E Reeve
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2008
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e3dce1b3efc54e1b8fb8d4532af840ea
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spelling	oai:doaj.org-article:e3dce1b3efc54e1b8fb8d4532af840ea2021-12-02T01:09:08ZHeterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition1177-54751177-5491https://doaj.org/article/e3dce1b3efc54e1b8fb8d4532af840ea2008-06-01T00:00:00Zhttp://www.dovepress.com/heterogeneous-gene-expression-changes-in-colorectal-cancer-cells-share-a1739https://doaj.org/toc/1177-5475https://doaj.org/toc/1177-5491Bostjan Humar1, Les McNoe1, Anita Dunbier1, Rosemary Heathcott1, Antony W Braithwaite2, Anthony E Reeve11Cancer Genetics Laboratory, Department of Biochemistry; University of Otago, Dunedin, Aotearoa New Zealand; 2Children&#39;s Medical Research Institute, Wintworthbill, NSW, AustraliaAbstract: Cyclooxygenase-2 (COX-2), the prostaglandin (PG)-synthesizing enzyme overexpressed in colorectal cancer (CRC), has pleiotropic, cancer-promoting effects. COX-2inhibitors (CIBs) interfere with many cancer-associated processes and show promising antineoplastic activity, however, a common mechanism of CIB action has not yet been established. We therefore investigated by microarray the global response towards the CIB APHS at a dose significantly inhibiting the growth of three COX-2-positive CRC but not of two COX-2-negative cell lines. None of the genes significantly (p = 0.005) affected by APHS were common to all three cell lines and 83% of the altered pathways were cell line-specific. Quantitative polymerase chain reaction (QPCR) on selected pathways confirmed cell line-specific expression alterations induced by APHS. A low stringency data analysis approach using BRB array tools coupled with QPCR, however, identified small expression changes shared by all COX-2-positive cell lines in genes related to the WNT pathway, the key driver of colonic carcinogenesis. Our data indicates a substantial cell line-specificity of APHS-induced expression alterations in CRC cells and helps to explain the divergent effects reported for CIBs. Further, the shared inhibition of the WNT pathway by APHS suggests one potential common mechanism behind the antineoplastic effects of COX-2 inhibition.Keywords: antineoplastic drugs, cell lines, colon cancer, COX-2 inhibitors, DNA arrays, WNT factors Bostjan HumarLes McNoeAnita DunbierRosemary HeathcottAntony W BraithwaiteAnthony E ReeveDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2008, Iss Issue 2, Pp 329-337 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Bostjan Humar Les McNoe Anita Dunbier Rosemary Heathcott Antony W Braithwaite Anthony E Reeve Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition
description	Bostjan Humar1, Les McNoe1, Anita Dunbier1, Rosemary Heathcott1, Antony W Braithwaite2, Anthony E Reeve11Cancer Genetics Laboratory, Department of Biochemistry; University of Otago, Dunedin, Aotearoa New Zealand; 2Children&#39;s Medical Research Institute, Wintworthbill, NSW, AustraliaAbstract: Cyclooxygenase-2 (COX-2), the prostaglandin (PG)-synthesizing enzyme overexpressed in colorectal cancer (CRC), has pleiotropic, cancer-promoting effects. COX-2inhibitors (CIBs) interfere with many cancer-associated processes and show promising antineoplastic activity, however, a common mechanism of CIB action has not yet been established. We therefore investigated by microarray the global response towards the CIB APHS at a dose significantly inhibiting the growth of three COX-2-positive CRC but not of two COX-2-negative cell lines. None of the genes significantly (p = 0.005) affected by APHS were common to all three cell lines and 83% of the altered pathways were cell line-specific. Quantitative polymerase chain reaction (QPCR) on selected pathways confirmed cell line-specific expression alterations induced by APHS. A low stringency data analysis approach using BRB array tools coupled with QPCR, however, identified small expression changes shared by all COX-2-positive cell lines in genes related to the WNT pathway, the key driver of colonic carcinogenesis. Our data indicates a substantial cell line-specificity of APHS-induced expression alterations in CRC cells and helps to explain the divergent effects reported for CIBs. Further, the shared inhibition of the WNT pathway by APHS suggests one potential common mechanism behind the antineoplastic effects of COX-2 inhibition.Keywords: antineoplastic drugs, cell lines, colon cancer, COX-2 inhibitors, DNA arrays, WNT factors
format	article
author	Bostjan Humar Les McNoe Anita Dunbier Rosemary Heathcott Antony W Braithwaite Anthony E Reeve
author_facet	Bostjan Humar Les McNoe Anita Dunbier Rosemary Heathcott Antony W Braithwaite Anthony E Reeve
author_sort	Bostjan Humar
title	Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition
title_short	Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition
title_full	Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition
title_fullStr	Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition
title_full_unstemmed	Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition
title_sort	heterogeneous gene expression changes in colorectal cancer cells share the wnt pathway in response to growth suppression by aphs-mediated cox-2 inhibition
publisher	Dove Medical Press
publishDate	2008
url	https://doaj.org/article/e3dce1b3efc54e1b8fb8d4532af840ea
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Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition

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