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Series GSE1417

Query DataSets for GSE1417

Status

Public on May 18, 2004

Title

Untreated vs. Camptothecin Treated HeLa cells

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

Pharmacogenomic identification of targets for adjuvant therapy with the topoisomerase poison camptothecin.

The response of tumor cells to the unusual form of DNA damage caused by topoisomerase poisons such as camptothecin (CPT) is poorly understood, and knowledge regarding which drugs can be effectively combined with CPT is lacking. To better understand the response of tumor cells to CPT and to identify potential targets for adjuvant therapy, we examined global changes in mRNA abundance in HeLa cells after CPT treatment using Affymetrix U133A GeneChips, which include all annotated human genes (22,283 probe sets). Statistical analysis of the data using a Bayesian/Cyber t test and a modified Benjamini and Hochberg correction for multiple hypotheses testing identified 188 probe sets that are induced and 495 that are repressed 8 h after CPT treatment at a False Discovery Rate of <0.05 and a minimum 3-fold change. This pharmacogenomic approach led us to identify two pathways that are CPT induced: (a) the epidermal growth factor receptor; and (b) nuclear factor-kappaB-regulated antiapoptotic factors. Experiments using HeLa cells in our lab and prior animal model studies performed elsewhere confirm that inhibitors of these respective pathways super-additively enhance CPT's cytotoxicity, suggesting their potential as targets for adjuvant therapy with CPT.

Cancer Res. 2004 Mar 15;64(6):2096-104
Keywords = HeLa
Keywords = Camptothecin
Keywords: ordered

Contributor(s)

Carson JP, Zhang N, Frampton GM, Gerry NP, Lenburg ME, Christman MF

Citation(s)

15026349

Submission date

May 18, 2004

Last update date

Aug 10, 2018

Contact name

Garrett M Frampton

E-mail(s)

[email protected]