Differentially expressed genes associated with CIS-diamminedichloroplatinum (II) resistance in head and neck cancer using differential display and CDNA microarray.
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.
Higuchi
Eisaku
E
Department of Otolaryngology-Head & Neck Surgery, Hokkaido University, Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan.
Oridate
Nobuhiko
N
Furuta
Yasushi
Y
Suzuki
Seigo
S
Hatakeyama
Hiromitsu
H
Sawa
Hirofumi
H
Sunayashiki-Kusuzaki
Kousaku
K
Yamazaki
Ken-Ichi
K
Inuyama
Yukio
Y
Fukuda
Satoshi
S
D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D018076:DNA, Complementary / Q000032:analysis*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation
D018076:DNA, Complementary; D005819:Genetic Markers; D008562:Membrane Glycoproteins; D002945:Cisplatin