Activation of PI3K/Akt signaling and hormone resistance in breast cancer

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著者

    • TOKUNAGA Eriko
    • Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
    • KIMURA Yasue
    • Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
    • MASHINO Kojiro
    • Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
    • OKI Eiji
    • Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
    • KATAOKA Akemi
    • Department of Breast Oncology, National Kyushu Cancer Center
    • OHNO Shinji
    • Department of Breast Oncology, National Kyushu Cancer Center
    • MORITA Masaru
    • Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
    • KAKEJI Yoshihiro
    • Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University
    • BABA Hideo
    • Department of Gastroenterological Surgery, Postgraduate School of Medicine, Kumamoto University
    • MAEHARA Yoshihiko
    • Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University

抄録

Akt is a serine/threonine kinase that has been demonstrated to play an important role in survival when cells are exposed to different apoptotic stimuli. Recent studies show that aberrant activation of Akt in breast carcinoma is associated with a poor prognosis and resistance to endocrine therapy and chemotherapy. The Akt signaling pathway is currently attracting considerable attention as a new target for effective therapeutic strategies. We investigated the incidence of Akt activation in 252 primary breast carcinomas and relationships among the activation of Akt, HER2 overexpression, hormone receptor expression, and alteration of the PTEN gene. Eighty-four cases (33.3%) were positive for pAkt expression. pAkt was significantly associated with HER2 overexpression (p<0.0001) and LOH at the PTEN gene locus (p<0.01). There was an inverse correlation between pAkt and PR (p<0.05). We also retrospectively examined the relationship between Akt activation and the efficacy of endocrine therapy for metastatic breast cancer. Of these 36 metastatic breast cancer cases, 12 cases (33.4%) were considered to show positive pAkt expression. In the pAkt-positive patients, endocrine therapy demonstrated worse efficacy than in pAkt-negative patients (p<0.01). In addition, the clinical benefit was the smallest in the patients positive both for HER2 and pAkt (p<0.01). The clinical benefit rate of estrogen deprivation therapy with AI or LH-RH agonist was significantly lower in the pAkt-positive patients than that in the pAkt-negative ones (p<0.05), and there was a tendency for the clinical benefit of SERM to be smaller in the pAkt-positive patients (p=0.09). These findings therefore suggest that Akt activation induces endocrine resistance in metastatic breast cancer, irrespective of the kind of endocrine agents that were administered. Our findings indicate that the activation of Akt in the downstream pathway of HER2 plays an important role in resistance to endocrine therapy for breast cancer. Our findings suggest that pAkt may be a useful predictor of resistance to endocrine therapy for breast cancer, while also suggesting that the inhibition of Akt may increase the efficacy of endocrine therapy.

収録刊行物

  • Breast cancer : the journal of the Japanese Breast Cancer Society  

    Breast cancer : the journal of the Japanese Breast Cancer Society 13(2), 137-144, 2006-04-10 

    The Japanese Breast Cancer Society

参考文献:  24件

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各種コード

  • NII論文ID(NAID)
    10018167738
  • NII書誌ID(NCID)
    AA1103354X
  • 本文言語コード
    ENG
  • 資料種別
    REV
  • ISSN
    13406868
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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