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Sökning: onr:"swepub:oai:lup.lub.lu.se:50be076f-13c6-46b2-bef1-aebd30836411" > PKA-induced phospho...

PKA-induced phosphorylation of ER alpha at serine 305 and high PAK1 levels is associated with sensitivity to tamoxifen in ER-positive breast cancer

Kok, Marleen (författare)
Netherlands Cancer Institute
Zwart, Wilbert (författare)
Netherlands Cancer Institute
Wigerup, Caroline (författare)
Lund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups
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Fles, Renske (författare)
Netherlands Cancer Institute
Hauptmann, Michael (författare)
Netherlands Cancer Institute
Van't Veer, Laura J. (författare)
Wessels, Lodewyk F. A. (författare)
Netherlands Cancer Institute
Neefjes, Jacques (författare)
Netherlands Cancer Institute
Stal, Olle (författare)
Linn, Sabine C. (författare)
Netherlands Cancer Institute
Landberg, Göran (författare)
Lund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups
Michalides, Rob (författare)
Netherlands Cancer Institute
Holm, Caroline (författare)
Lund University
Landberg, Goran (författare)
Lund University
Vant Veer, LauraJ. (författare)
Netherlands Cancer Institute
Stål, Olle (författare)
Östergötlands Läns Landsting,Linköpings universitet,Onkologi,Hälsouniversitetet,Onkologiska kliniken US
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 (creator_code:org_t)
Springer, 2011
2011
Engelska.
Ingår i: Breast Cancer Research and Treatment. - : Springer. - 1573-7217 .- 0167-6806. ; 125:1, s. 1-12
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Phosphorylation of estrogen receptor alpha at serine 305 (ER alpha S305-P) by protein kinase A (PKA) or p21-activated kinase 1 (PAK1) has experimentally been associated with tamoxifen sensitivity. Here, we investigated the clinical application of this knowledge to predict tamoxifen resistance in ER-positive breast cancer patients. Using immunohistochemistry, a score including PAK1 and co-expression of PKA and ER alpha S305-P (PKA/ER alpha S305-P) was developed on a training set consisting of 103 patients treated with tamoxifen for metastatic disease, and validated on 231 patients randomized between adjuvant tamoxifen or no treatment. In the training set, PAK1 levels were associated with tumor progression after tamoxifen (HR 1.57, 95% CI 0.99-2.48), as was co-expression of PKA and ER alpha S305-P (HR 2.00, 95% CI 1.14-3.52). In the validation set, a significant tamoxifen benefit was found among the 73% patients negative for PAK1 and PKA/ER alpha S305-P (HR 0.54, 95% CI 0.34-0.87), while others (27%) were likely to have no benefit from tamoxifen (HR 0.88, 95% 0.42-1.82). The test for interaction showed a significant difference in recurrence-free survival between groups defined by PAK1 and PKA/ER alpha S305-P (P = 0.037). Elevated PAK1 and PKA/ER alpha S305-P appeared to influence tamoxifen sensitivity. Both PAK1 and PKA/ER alpha S305-P levels were associated with sensitivity to tamoxifen in breast tumors and the combination of these variables should be considered in predicting tamoxifen benefit.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

Tamoxifen sensitivity
Phosphorylation of ER
PKA
PAK1
Breast cancer
PKA; PAK1; Phosphorylation of ER; Tamoxifen sensitivity; Breast cancer
MEDICINE
MEDICIN

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