Premium
Akt is frequently activated in HER2/neu‐positive breast cancers and associated with poor prognosis among hormone‐treated patients
Author(s) -
Tokunaga Eriko,
Kimura Yasue,
Oki Eiji,
Ueda Naoyuki,
Futatsugi Motonori,
Mashino Kojiro,
Yamamoto Manabu,
Ikebe Masahiko,
Kakeji Yoshihiro,
Baba Hideo,
Maehara Yoshihiko
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21358
Subject(s) - protein kinase b , medicine , breast cancer , her2/neu , oncology , hormone therapy , hormone , cancer , adjuvant therapy , breast carcinoma , hormonal therapy , pi3k/akt/mtor pathway , cancer research , signal transduction , biology , biochemistry
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. © 2005 Wiley‐Liss, Inc.