TY - JOUR
T1 - Activated Akt expression in breast cancer
T2 - Correlation with p53, Hdm2 and patient outcome
AU - Vestey, S. B.
AU - Sen, C.
AU - Calder, C. J.
AU - Perks, C. M.
AU - Pignatelli, M.
AU - Winters, Z. E.
N1 - Funding Information:
This work was funded by the University of Bristol Cancer Research Committee, the Joan Greenfield Fellowship and the United Bristol Healthcare NHS Trust Medical Research Committee. S.B. Vestey was the recipient of a Ronald Raven Travelling Fellowship.
PY - 2005/5
Y1 - 2005/5
N2 - Activation of protein kinase-B/Akt (pAkt) is mediated by oestrogen and involves HER-2 in vitro, to phosphorylate Hdm2 and influence p53 cytoplasmic localisation and degradation. Expression of all active Akt isoforms (pAkt) were examined, together with p53/Hdm2 subcellular expression in invasive ductal breast cancers (IDCs), to evaluate whether in vitro findings were related to clinical data and determine the effect on outcome. Immunohistochemical expression of serine 473 specific phosphorylated Akt (pAkt) isoforms (Akt-1,2,3) was evaluated in 97 patients, together with subcellular expression of p53/Hdm2. The results show that pAkt was evaluable in 95 patients with cytoplasmic expression in 81% and more likely to be associated with larger tumours (P = 0.007), with no correlation with HER-2 expression. pAkt correlated with increasing levels of cytoplasmic p53 (P = 0.025) and was associated with a reduced disease-free survival (P = 0.04; univariate). In conclusion, pAkt has implications in breast cancer growth through mechanisms inactivating p53 with an association with immunohistochemical p53 expression, which is preferentially cytoplasmic. Despite in vitro associations, pAkt appears to be a variable marker of HER-2 expression.
AB - Activation of protein kinase-B/Akt (pAkt) is mediated by oestrogen and involves HER-2 in vitro, to phosphorylate Hdm2 and influence p53 cytoplasmic localisation and degradation. Expression of all active Akt isoforms (pAkt) were examined, together with p53/Hdm2 subcellular expression in invasive ductal breast cancers (IDCs), to evaluate whether in vitro findings were related to clinical data and determine the effect on outcome. Immunohistochemical expression of serine 473 specific phosphorylated Akt (pAkt) isoforms (Akt-1,2,3) was evaluated in 97 patients, together with subcellular expression of p53/Hdm2. The results show that pAkt was evaluable in 95 patients with cytoplasmic expression in 81% and more likely to be associated with larger tumours (P = 0.007), with no correlation with HER-2 expression. pAkt correlated with increasing levels of cytoplasmic p53 (P = 0.025) and was associated with a reduced disease-free survival (P = 0.04; univariate). In conclusion, pAkt has implications in breast cancer growth through mechanisms inactivating p53 with an association with immunohistochemical p53 expression, which is preferentially cytoplasmic. Despite in vitro associations, pAkt appears to be a variable marker of HER-2 expression.
KW - HER-2
KW - Hdm2
KW - Immunohistochemistry
KW - Phospho-Akt
KW - p53
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U2 - 10.1016/j.ejca.2005.02.011
DO - 10.1016/j.ejca.2005.02.011
M3 - Article
C2 - 15862750
AN - SCOPUS:18044373883
SN - 0959-8049
VL - 41
SP - 1017
EP - 1025
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 7
ER -
