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Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth

Bostjan Humar1, Les McNoe, Anita Dunbier

  • 1Cancer Genetics Laboratory, Department of Biochemistry; University of Otago, Dunedin, Aotearoa New Zealand;

Biologics : Targets & Therapy
|August 27, 2009
PubMed

Insights

Cyclooxygenase-2 (COX-2) inhibitors show antineoplastic activity in colorectal cancer (CRC). APHS affects cell lines differently, but commonly inhibits the WNT pathway in COX-2-positive CRC, suggesting a shared anticancer mechanism.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cyclooxygenase-2 (COX-2) is overexpressed in colorectal cancer (CRC) and promotes tumor growth.
  • COX-2 inhibitors (CIBs) exhibit antineoplastic effects, but their common mechanism of action remains unclear.

Purpose of the Study:

  • To investigate the global gene expression response to the CIB APHS in CRC cell lines.
  • To identify common mechanisms of CIB action, particularly in COX-2-positive CRC.

Main Methods:

  • Microarray analysis of gene expression in CRC cell lines treated with APHS.
  • Quantitative polymerase chain reaction (QPCR) for validating gene expression changes.
  • BRB array tools for low stringency data analysis.

Main Results:

  • APHS induced significant gene expression alterations, with 83% of affected pathways being cell line-specific.
  • No common significantly affected genes were found across all cell lines.
  • A shared, albeit small, expression change in WNT pathway genes was identified in COX-2-positive CRC cells.

Conclusions:

  • APHS exhibits substantial cell line-specific effects in CRC.
  • The shared inhibition of the WNT pathway by APHS may represent a common mechanism for COX-2 inhibitor antineoplastic activity in CRC.
Keywords:
COX-2 inhibitorsDNA arraysWNT factorsantineoplastic drugscell linescolon cancer

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