Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients

Eriko Tokunaga, Yasue Kimura, Eiji Oki, Naoyuki Ueda, Motonori Futatsugi, Kojiro Mashino, Manabu Yamamoto, Masahiko Ikebe, Yoshihiro Kakeji, Hideo Baba, Yoshihiko Maehara

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Akt/PKB is a serine/threonine kinase that plays an important role in survival when cells are exposed to different apoptotic stimuli. Aberrant activation of Akt/PKB in breast carcinoma is associated with poor prognosis and resistance to endocrine therapy and chemotherapy. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Breast cancer tissues obtained from 252 patients were utilized for this study. We evaluated Akt activation by immunohistochemical assessment of the expression of phosphorylated Akt (pAkt) at Ser-473. Eighty-four cases (33.3%) were diagnosed as positive for pAkt expression. pAkt was significantly associated with HER2/neu overexpression (p < 0.0001). There was an inverse correlation between pAkt and PR expression (p = 0.0321); however, there was no association between pAkt and ER expression. Survival analysis showed that pAkt positivity was associated with poor disease-free survival in cases with postoperative hormone therapy; however, there was no association in cases without hormone therapy. Our results indicate that Akt activation induced poor prognosis in patients who received adjuvant hormone therapy. This finding suggests that inhibition of the Akt signaling pathway may increase the efficacy of hormone therapy and improve the prognosis of patients who receive adjuvant hormone therapy.

Original languageEnglish
Pages (from-to)284-289
Number of pages6
JournalInternational Journal of Cancer
Volume118
Issue number2
DOIs
Publication statusPublished - Jan 15 2006

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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