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PMID: 11870534 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients.

British journal of cancer ·Vol. 86 ·No. 4 ·2002-02-12 ·Pages 540-5

Pérez-Tenorio G, Stål O, Southeast Sweden Breast Cancer Group

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.

MeSH Terms
Adult Antineoplastic Agents, Hormonal/therapeutic use Breast Neoplasms/drug therapy,metabolism,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
Chemicals
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
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pérez-Tenorio G
Department of Biomedicine and Surgery, Division of Oncology, Clinical Research Center, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. gizpe@ibk.liu.se
Stål O
Southeast Sweden Breast Cancer Group
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/sj.bjc.6600126
Email
gizpe@ibk.liu.se
Published
2002-02-12
Pages
540-5
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2375266
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjc.6600126 PMC Full Text View journal details
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