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Differentially expressed genes associated with CIS-diamminedichloroplatinum (II) resistance in head and neck cancer
Eisaku Higuchi1, Nobuhiko Oridate, Yasushi Furuta
1Department of Otolaryngology-Head & Neck Surgery, Hokkaido University, Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.
Background:
The mechanism by which cancer cells become resistant to cis-Diamminedichloroplatinum (II) (cDDP) is not completely understood. To investigate the molecular markers involved in the cDDP resistance, we compared the gene expression profiles between a head and neck squamous cell carcinoma (HNSCC) line sensitive to cDDP and its cDDP-resistant variant.
Methods:
Both a fluorescent differential display and a cDNA microarray analysis were applied to distinguish the gene profiles between KB, a human HNSCC line, and its cDDP-resistant variant (KB/cDDP). These results were confirmed by Northern blot analysis.
Results:
One up-regulated gene, glycoprotein hormone alpha-subunit, and two down-regulated genes coding membrane proteins, human folate receptor and tumor-associated antigen L6, were identified in KB/cDDP cells.
Conclusions:
Our findings suggest that development of the cDDP-resistant phenotype is accompanied by alternations of gene expression including a glycoprotein hormone and membrane proteins. These gene products could be new molecular markers for resistance to cDDP.
Insights
Understanding cis-Diamminedichloroplatinum (II) (cDDP) resistance in head and neck cancer is crucial. This study identified specific gene expression changes, including glycoprotein hormone and membrane proteins, associated with cDDP resistance in HNSCC cells.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- The mechanisms underlying cis-Diamminedichloroplatinum (II) (cDDP) resistance in cancer remain incompletely elucidated.
- cis-Diamminedichloroplatinum (II) (cDDP) is a cornerstone chemotherapy agent for various cancers, including head and neck squamous cell carcinoma (HNSCC).
- Acquired resistance to cDDP significantly limits therapeutic efficacy.
Purpose of the Study:
- To investigate the molecular markers associated with cDDP resistance in HNSCC.
- To compare gene expression profiles between cDDP-sensitive and cDDP-resistant HNSCC cell lines.
Main Methods:
- Utilized fluorescent differential display and cDNA microarray analysis to compare gene expression.
- Employed a human HNSCC cell line (KB) and its cDDP-resistant variant (KB/cDDP).
- Confirmed differential gene expression using Northern blot analysis.
Main Results:
- Identified one up-regulated gene: glycoprotein hormone alpha-subunit.
- Identified two down-regulated genes encoding membrane proteins: human folate receptor and tumor-associated antigen L6.
- These molecular alterations were observed in the cDDP-resistant KB/cDDP cells.
Conclusions:
- The development of cDDP resistance in HNSCC is associated with significant alterations in gene expression.
- Glycoprotein hormone and specific membrane proteins (folate receptor, antigen L6) are implicated in cDDP resistance.
- These identified gene products represent potential novel molecular markers for predicting or overcoming cDDP resistance.