TY - JOUR
T1 - Enhanced expression of nuclear factor I/B in oxaliplatin-resistant human cancer cell lines
AU - Kashiwagi, Eiji
AU - Izumi, Hiroto
AU - Yasuniwa, Yoshihiro
AU - Baba, Ryoko
AU - Doi, Yoshiaki
AU - Kidani, Akihiko
AU - Arao, Tokuzo
AU - Nishio, Kazuto
AU - Naito, Seiji
AU - Kohno, Kimitoshi
PY - 2011/2
Y1 - 2011/2
N2 - Oxaliplatin is a third-generation platinum drug that has favorable activity in cisplatin-resistant cells. However, the molecular mechanisms underlying oxaliplatin resistance are not well understood. To investigate the molecular mechanisms involved, resistant cell lines were independently derived from colon cancer (DLD1) and bladder cancer (T24) cells. Oxaliplatin-resistant DLD1 OX1 and DLD1 OX2 cell lines were approximately 16.3-fold and 17.8-fold more resistant to oxaliplatin than the parent cell lines, respectively, and had 1.7- and 2.2-fold higher cross-resistance to cisplatin, respectively. Oxaliplatin-resistant T24 OX2 and T24 OX3 cell lines were approximately 5.0-fold more resistant to oxaliplatin than the parent cell line and had 1.9-fold higher cross-resistance to cisplatin. One hundred and fifty-eight genes commonly upregulated in both DLD1 OX1 and DLD1 OX2 were identified by microarray analysis. These genes were mainly involved in the function of transcriptional regulators (14.6%), metabolic molecules (14.6%), and transporters (9.5%). Of these, nuclear factor I/B (NFIB) was upregulated in all oxaliplatin-resistant cells. Downregulation of NFIB rendered cells sensitive to oxaliplatin, but not to cisplatin. Forced expression of NFIB induced resistance to oxaliplatin, but not to cisplatin. Taken together, these results suggest that NFIB is a novel and specific biomarker for oxaliplatin resistance in human cancers.
AB - Oxaliplatin is a third-generation platinum drug that has favorable activity in cisplatin-resistant cells. However, the molecular mechanisms underlying oxaliplatin resistance are not well understood. To investigate the molecular mechanisms involved, resistant cell lines were independently derived from colon cancer (DLD1) and bladder cancer (T24) cells. Oxaliplatin-resistant DLD1 OX1 and DLD1 OX2 cell lines were approximately 16.3-fold and 17.8-fold more resistant to oxaliplatin than the parent cell lines, respectively, and had 1.7- and 2.2-fold higher cross-resistance to cisplatin, respectively. Oxaliplatin-resistant T24 OX2 and T24 OX3 cell lines were approximately 5.0-fold more resistant to oxaliplatin than the parent cell line and had 1.9-fold higher cross-resistance to cisplatin. One hundred and fifty-eight genes commonly upregulated in both DLD1 OX1 and DLD1 OX2 were identified by microarray analysis. These genes were mainly involved in the function of transcriptional regulators (14.6%), metabolic molecules (14.6%), and transporters (9.5%). Of these, nuclear factor I/B (NFIB) was upregulated in all oxaliplatin-resistant cells. Downregulation of NFIB rendered cells sensitive to oxaliplatin, but not to cisplatin. Forced expression of NFIB induced resistance to oxaliplatin, but not to cisplatin. Taken together, these results suggest that NFIB is a novel and specific biomarker for oxaliplatin resistance in human cancers.
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U2 - 10.1111/j.1349-7006.2010.01784.x
DO - 10.1111/j.1349-7006.2010.01784.x
M3 - Article
C2 - 21087353
AN - SCOPUS:79952083052
SN - 1347-9032
VL - 102
SP - 382
EP - 386
JO - Cancer Science
JF - Cancer Science
IS - 2
ER -
