Activation of Akt signaling pathway has been
documented in various human malignancies, including breast
carcinoma. The objective of this study is to determine the
incidence of Akt phosphorylation in breast tumours and its
relationship with expression of ER-α, ER-β, HER2, Ki-67
and phosphorylated Bcl-2 associated death domain (p-BAD).
Immunohistochemical staining was performed to detect these
molecules on 43 paraffin-embedded breast tumour tissues
with commercially available antibodies. Eighteen (41.9%), 3
(7.0%), 23 (53.5%), 35 (81.4%), 21 (48.8%), 29 (67.4%), and
34 (81.0%) of breast tumours were positive for nuclear ER-α,
nuclear ER-β, membranous HER2, cytonuclear p-Akt
(Thr308), p-Akt (Ser473), p-BAD and Ki-67, respectively.
ER-α expression was inversely correlated with HER2 and
Ki-67 (P=0.041 and P=0.040, respectively). The p-Akt
(Ser473) was correlated with increased level of p-BAD
(Ser136) (P=0.012). No relationship of Akt phosphorylation
with HER2, ER-α or ER-β was found. The p-Akt (Ser473)
immunoreactivity was significantly higher in stage IV than in stage I or II (P=0.036 or P=0.009). The higher Ki-67 and lower ER-α expression showed an association with patient
age of <50 years (P=0.004) and with positive nodal status
(P=0.033), respectively. Our data suggest that the Akt
phosphorylation and inactivation of its downstream target,
BAD may play a role in survival of breast cancer cell. This
study does not support the simple model of linear HER2/
PI3K/Akt pathway in breast cancer.