TY - JOUR
T1 - A BTB/POZ gene, NAC-1, a tumor recurrence-associated gene, as a potential target fortaxol resistance in ovarian cancer
AU - Ishibashi, Masako
AU - Nakayama, Kentaro
AU - Yeasmin, Shamima
AU - Katagiri, Atsuko
AU - Iida, Kouji
AU - Nakayama, Naomi
AU - Fukumoto, Manabu
AU - Miyazaki, Kohji
PY - 2008/5/15
Y1 - 2008/5/15
N2 - Purpose: We previously determined that NAC-1, a transcription factor and member of the BTB/POZ gene family, is associated with recurrent ovarian carcinomas. In the current study, we investigated further the relationship between NAC-1 expression and ovarian cancer. Experimental Design: NAC-1 expression was assessed by immunohistochemistry, and clinical variables were collected by retrospective chart review. SiRNA system and NAC-1 gene trans-fection were used to asses NAC-1 function in Taxol resistance in vivo. Results: Overexpression of NAC-1 correlated with shorter relapse-free survival in patients with advanced stage (stage lll/IV) ovarian carcinoma treated with platinum and taxane chemotherapy. Furthermore, overexpression of NAC-1 in primary tumors predicted recurrence within 6 months after primary cytoreductive surgery followed by standard platinum and taxane chemotherapy. NAC-1 expression levels were measured and compared among the human ovarian cancer cell line (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel-resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to dose-escalating paclitaxel. Overexpression of NAC-1 was observed in only theTaxol-resistant KF28TX and KFr13 TX cells but not in KF28 or cisplatin-resistant KFr13 cells. To confirm that NAC-1 expression was related to Taxol resistance, we used two independent but complementary approaches. NAC-1 gene knockdown in both KF28TX and KFr13TX rescued paclitaxel sensitivity. Additionally, engineered expression of NAC-1 in RK3E cells induced paclitaxel resistance. Conclusions: These results suggest that NAC-1 regulates Taxol resistance in ovarian cancer and may provide an effective target for chemotherapeutic intervention inTaxol-resistant tumors.
AB - Purpose: We previously determined that NAC-1, a transcription factor and member of the BTB/POZ gene family, is associated with recurrent ovarian carcinomas. In the current study, we investigated further the relationship between NAC-1 expression and ovarian cancer. Experimental Design: NAC-1 expression was assessed by immunohistochemistry, and clinical variables were collected by retrospective chart review. SiRNA system and NAC-1 gene trans-fection were used to asses NAC-1 function in Taxol resistance in vivo. Results: Overexpression of NAC-1 correlated with shorter relapse-free survival in patients with advanced stage (stage lll/IV) ovarian carcinoma treated with platinum and taxane chemotherapy. Furthermore, overexpression of NAC-1 in primary tumors predicted recurrence within 6 months after primary cytoreductive surgery followed by standard platinum and taxane chemotherapy. NAC-1 expression levels were measured and compared among the human ovarian cancer cell line (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel-resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to dose-escalating paclitaxel. Overexpression of NAC-1 was observed in only theTaxol-resistant KF28TX and KFr13 TX cells but not in KF28 or cisplatin-resistant KFr13 cells. To confirm that NAC-1 expression was related to Taxol resistance, we used two independent but complementary approaches. NAC-1 gene knockdown in both KF28TX and KFr13TX rescued paclitaxel sensitivity. Additionally, engineered expression of NAC-1 in RK3E cells induced paclitaxel resistance. Conclusions: These results suggest that NAC-1 regulates Taxol resistance in ovarian cancer and may provide an effective target for chemotherapeutic intervention inTaxol-resistant tumors.
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U2 - 10.1158/1078-0432.CCR-07-4358
DO - 10.1158/1078-0432.CCR-07-4358
M3 - Article
C2 - 18483383
AN - SCOPUS:49649116153
VL - 14
SP - 3149
EP - 3155
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 10
ER -