Activation of AKT/PKB in Breast Cancer Predicts a Worse Outcome Among Endocrine Treated Patients

Br J Cancer. 2002 Feb 12;86(4):540-5. doi: 10.1038/sj.bjc.6600126.

Abstract

Akt/PKB is a serine/threonine protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival in association with tyrosine kinase receptors. The protein is a downstream effector of erbB-2 with implications in breast cancer progression and drug resistance in vitro. We aimed to examine the role of Akt-1 in breast cancer patients, by determining whether the expression (Akt-1) and/or activation (pAkt) were related to prognostic markers and survival. The expression of erbB-2, heregulin beta 1 and Bcl-2 was also assessed by flow cytometry or immunohistochemistry. This study comprised 93 patients, aged <50 who were treated with tamoxifen and/or goserelin. We found that pAkt was associated with lower S-phase fraction (P=0.001) and the presence of heregulin beta 1-expressing stromal cells (P=0.017). Neither Akt-1 nor pAkt was related with other factors. Tumour cells-derived heregulin beta 1 was found mainly in oestrogen receptor negative (P=0.026) and node negative (P=0.005) cases. Survival analysis revealed that pAkt positive patients were more prone to relapse with distant metastasis, independently of S-phase fraction and nodal status (multivariate analysis; P=0.004). The results suggest that activation of Akt may have prognostic relevance in breast cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • DNA, Neoplasm / analysis
  • Disease-Free Survival
  • Female
  • Flow Cytometry
  • Goserelin / therapeutic use*
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Neuregulin-1 / metabolism
  • Prognosis
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptor, ErbB-2 / metabolism
  • S Phase
  • Survival Rate
  • Tamoxifen / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Hormonal
  • DNA, Neoplasm
  • Neuregulin-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tamoxifen
  • Goserelin
  • heregulin beta1
  • Receptor, ErbB-2
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt