Overexpression of class III β-tubulin predicts good response to taxane-based chemotherapy in ovarian clear cell adenocarcinoma

Daisuke Aoki, Yoshinao Oda, Satoshi Hattori, Ken Ichi Taguchi, Yoshihiro Ohishi, Yuji Basaki, Shinji Oie, Nao Suzuki, Suminori Kono, Masazumi Tsuneyoshi, Mayumi Ono, Takashi Yanagawa, Michihiko Kuwano

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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 languageEnglish
Pages (from-to)1473-1480
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number4
DOIs
Publication statusPublished - Feb 15 2009

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Clear Cell Adenocarcinoma
Tubulin
Stathmin
Drug Therapy
Microtubules
Ovarian Neoplasms
RNA Isoforms
taxane
Cell Line
Paclitaxel
Drug Resistance
Small Interfering RNA
Research Design
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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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 journalArticle

Aoki, D, Oda, Y, Hattori, S, Taguchi, KI, Ohishi, Y, Basaki, Y, Oie, S, Suzuki, N, Kono, S, Tsuneyoshi, M, Ono, M, Yanagawa, T & Kuwano, M 2009, 'Overexpression of class III β-tubulin predicts good response to taxane-based chemotherapy in ovarian clear cell adenocarcinoma', Clinical Cancer Research, vol. 15, no. 4, pp. 1473-1480. https://doi.org/10.1158/1078-0432.CCR-08-1274
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. / Overexpression of class III β-tubulin predicts good response to taxane-based chemotherapy in ovarian clear cell adenocarcinoma. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 4. pp. 1473-1480.
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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

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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.

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