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Akt kinases in brea...
Akt kinases in breast cancer and the results of adjuvant therapy
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- Stål, Olle (författare)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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- Perez-Tenorio, Gizeh (författare)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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Åkerberg, Lind (författare)
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- Olsson, Birgit (författare)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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- Nordenskjöld, Bo (författare)
- Linköpings universitet,Onkologi,Hälsouniversitetet
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- Skoog, Lambert (författare)
- Karolinska Institutet
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- Rutqvist, Lars (författare)
- Department of Oncology, Huddinge University Hospital, Stockholm, Sweden
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(creator_code:org_t)
- 2003-04-01
- 2003
- Engelska.
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 5:2, s. R37-R44
- Relaterad länk:
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https://breast-cance...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- BackgroundThe serine/threonine kinase Akt, or protein kinase B, has recently been a focus of interest because of its activity to inhibit apoptosis. It mediates cell survival by acting as a transducer of signals from growth factor receptors that activate phosphatidylinositol 3-kinase.MethodsWe analysed the expression of the isoforms Akt1 and Akt2 as well as phosphorylated Akt (pAkt) by immunohistochemistry in frozen tumour samples from 280 postmenopausal patients who participated in a randomised trial comparing cyclophosphamide–methotrexate–5-fluorouracil chemotherapy and postoperative radiotherapy. The patients were simultaneously randomised to tamoxifen or to no endocrine treatment.ResultsMarked staining was found in 24% of the tumours for Akt1, but in only 4% for Akt2. A low frequency of Akt2-positive cells (1–10%) was observed in another 26% of the tumours. pAkt was significantly associated with both Akt1 and Akt2 expression. Overexpression of erbB2 correlated significantly with pAkt (P = 0.0028). The benefit from tamoxifen was analysed in oestrogen receptor (ER)-positive patients. Patients with a negative status of Akt (no overexpression of Akt1, Akt2 or pAkt) showed significant benefit from tamoxifen. The relative rate of distant recurrence, with versus without tamoxifen, was 0.44 (95% confidence interval [CI], 0.25–0.79) for ER+/Akt1- patients, while it was 0.72 (95% CI, 0.34–1.53) for ER+/Akt1+ patients. The difference in rate ratio did not reach statistical significance. The rate of locoregional recurrence was significantly decreased with radiotherapy versus chemotherapy for Akt-negative patients (rate ratio, 0.23; 95% CI, 0.08–0.67; P = 0.0074), while no benefit was evident for the Akt-positive subgroup (rate ratio, 0.77; 95% CI, 0.31–1.9; P = 0.58). The interaction between Akt and the efficacy of radiotherapy was significant in multivariate analysis (P = 0.042).ConclusionActivation of the Akt pathway is correlated with erbB2 overexpression in breast cancer. The results suggest that Akt may predict the local control benefit from radiotherapy.
Nyckelord
- erbB2
- HER-2/neu
- protein kinase B
- radiotherapy
- tamoxifen
- treatment outcome
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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