Gefitinib-related gene signature in bladder cancer cells identified by a cDNA microarray.
BACKGROUND
The aim of this study was to identify key genes linked to the molecular action of gefitinib, a promising anticancer agent on human bladder cancer cell lines.


METHODS
cDNA microarrays were used to profile feature genes in 5637 and T24 cells before and after treatment with gefitinib. PCR-based direct sequencing and Western blot analysis were performed to examine the mutation status and protein levels of EGFR in the cell lines.


RESULTS
Gefitinib significantly inhibited the proliferation of 5637 cells, while showing little inhibitory effect on T24 cells. Theses effects were independent of the mutation status and protein levels of EGFR. cDNA microarray analysis identified 15 feature genes classified as a cell cycle, apoptotic pathway and transcription. Notably, levels of expression of the cell invasion-related genes, YY1 and E-cadherin, were increased in 5637 cells sensitive to gefitinib.


CONCLUSIONS
Unique genes involved in the action of gefitinib were identified. Particularly, the upregulation of YY1 and E-cadherin may account for the efficacy of gefitinib in bladder cancer.
Inoue
Ryo
R
Department of Urology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Matsuyama
Hideyasu
H
Yano
Seiji
S
Yamamoto
Yoshiaki
Y
Iizuka
Norio
N
Naito
Katsusuke
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018076:DNA, Complementary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011799:Quinazolines / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D000970:Antineoplastic Agents; D018076:DNA, Complementary; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib