Abstract
Purpose: Of the various microtubule-associated molecules, β-tubulin 111 has been reported to be closely associated with the therapeutic efficacy of taxane-based chemotherapy against ovarian cancer. Stathmin and microtubule-associated protein 4 (MAP4) have been reported to play an important role in microtubule stabilization. In this study, we investigated whether expression of these microtubule-associated factors affects the therapeutic efficacy of taxane-based chemotherapy in ovarian clear cell adenocarcinoma. Experimental Design: Drug sensitivity of paclitaxel or cisplatin was assessed in ovarian cancer cell lines treated with small interfering RNA of tubulin isoforms, MAP4, and stathmin. We examined 94 surgically resected ovarian clear cell adenocarcinoma specimens from patients treated with taxane-containing regimens (n = 44) and with taxane-free regimens (n = 50), using immunohistochemistry to detect expression of β-tubulin III, stathmin, and MAP4, Results: Knockdown of β-tubulin III and IV specifically conferred drug resistance to paclitaxel in one ovarian cancer cell line, but not to other molecules. Estimated overall survival revealed a significant synergistic effect between taxane and β-tubulin III in patients with ovarian clear cell adenocarcinoma. Of three microtubule-related molecules, among the taxane-based chemotherapy group, cases with higher β-tubulin III expression were associated with a significantly more favorable prognosis compared with those having lower β-tubulin III expression. By contrast, there was no statistical significance in the synergistic relationships between stathmin and taxane or between MAP4 and taxane. Conclusions: Taxane-based chemotherapy was effective for patients with ovarian clear cell adenocarcinomas who were positive for β-tubulin III but not for those who were negative for these proteins.
| Original language | English |
|---|---|
| Pages (from-to) | 1473-1480 |
| Number of pages | 8 |
| Journal | Clinical Cancer Research |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2009 Feb 15 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Overexpression of class III β-tubulin predicts good response to taxane-based chemotherapy in ovarian clear cell adenocarcinoma. / Aoki, Daisuke; Oda, Yoshinao; Hattori, Satoshi; Taguchi, Ken Ichi; Ohishi, Yoshihiro; Basaki, Yuji; Oie, Shinji; Suzuki, Nao; Kono, Suminori; Tsuneyoshi, Masazumi; Ono, Mayumi; Yanagawa, Takashi; Kuwano, Michihiko.
In: Clinical Cancer Research, Vol. 15, No. 4, 15.02.2009, p. 1473-1480.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Overexpression of class III β-tubulin predicts good response to taxane-based chemotherapy in ovarian clear cell adenocarcinoma
AU - Aoki, Daisuke
AU - Oda, Yoshinao
AU - Hattori, Satoshi
AU - Taguchi, Ken Ichi
AU - Ohishi, Yoshihiro
AU - Basaki, Yuji
AU - Oie, Shinji
AU - Suzuki, Nao
AU - Kono, Suminori
AU - Tsuneyoshi, Masazumi
AU - Ono, Mayumi
AU - Yanagawa, Takashi
AU - Kuwano, Michihiko
PY - 2009/2/15
Y1 - 2009/2/15
N2 - Purpose: Of the various microtubule-associated molecules, β-tubulin 111 has been reported to be closely associated with the therapeutic efficacy of taxane-based chemotherapy against ovarian cancer. Stathmin and microtubule-associated protein 4 (MAP4) have been reported to play an important role in microtubule stabilization. In this study, we investigated whether expression of these microtubule-associated factors affects the therapeutic efficacy of taxane-based chemotherapy in ovarian clear cell adenocarcinoma. Experimental Design: Drug sensitivity of paclitaxel or cisplatin was assessed in ovarian cancer cell lines treated with small interfering RNA of tubulin isoforms, MAP4, and stathmin. We examined 94 surgically resected ovarian clear cell adenocarcinoma specimens from patients treated with taxane-containing regimens (n = 44) and with taxane-free regimens (n = 50), using immunohistochemistry to detect expression of β-tubulin III, stathmin, and MAP4, Results: Knockdown of β-tubulin III and IV specifically conferred drug resistance to paclitaxel in one ovarian cancer cell line, but not to other molecules. Estimated overall survival revealed a significant synergistic effect between taxane and β-tubulin III in patients with ovarian clear cell adenocarcinoma. Of three microtubule-related molecules, among the taxane-based chemotherapy group, cases with higher β-tubulin III expression were associated with a significantly more favorable prognosis compared with those having lower β-tubulin III expression. By contrast, there was no statistical significance in the synergistic relationships between stathmin and taxane or between MAP4 and taxane. Conclusions: Taxane-based chemotherapy was effective for patients with ovarian clear cell adenocarcinomas who were positive for β-tubulin III but not for those who were negative for these proteins.
AB - Purpose: Of the various microtubule-associated molecules, β-tubulin 111 has been reported to be closely associated with the therapeutic efficacy of taxane-based chemotherapy against ovarian cancer. Stathmin and microtubule-associated protein 4 (MAP4) have been reported to play an important role in microtubule stabilization. In this study, we investigated whether expression of these microtubule-associated factors affects the therapeutic efficacy of taxane-based chemotherapy in ovarian clear cell adenocarcinoma. Experimental Design: Drug sensitivity of paclitaxel or cisplatin was assessed in ovarian cancer cell lines treated with small interfering RNA of tubulin isoforms, MAP4, and stathmin. We examined 94 surgically resected ovarian clear cell adenocarcinoma specimens from patients treated with taxane-containing regimens (n = 44) and with taxane-free regimens (n = 50), using immunohistochemistry to detect expression of β-tubulin III, stathmin, and MAP4, Results: Knockdown of β-tubulin III and IV specifically conferred drug resistance to paclitaxel in one ovarian cancer cell line, but not to other molecules. Estimated overall survival revealed a significant synergistic effect between taxane and β-tubulin III in patients with ovarian clear cell adenocarcinoma. Of three microtubule-related molecules, among the taxane-based chemotherapy group, cases with higher β-tubulin III expression were associated with a significantly more favorable prognosis compared with those having lower β-tubulin III expression. By contrast, there was no statistical significance in the synergistic relationships between stathmin and taxane or between MAP4 and taxane. Conclusions: Taxane-based chemotherapy was effective for patients with ovarian clear cell adenocarcinomas who were positive for β-tubulin III but not for those who were negative for these proteins.
UR - http://www.scopus.com/inward/record.url?scp=63149086677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63149086677&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-1274
DO - 10.1158/1078-0432.CCR-08-1274
M3 - Article
C2 - 19228748
AN - SCOPUS:63149086677
VL - 15
SP - 1473
EP - 1480
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 4
ER -