Activated Akt expression in breast cancer: correlation with p53, Hdm2 and patient outcome.
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.
Vestey
S B
SB
University of Bristol, Department of Clinical Sciences at South Bristol--Surgery, Level 7, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK.
Sen
C
C
Calder
C J
CJ
Perks
C M
CM
Pignatelli
M
M
Winters
Z E
ZE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism*; D005260:Female; D015696:Gene Products, tat / Q000378:metabolism*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D015696:Gene Products, tat; D005819:Genetic Markers; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C470303:Tat-anti-HDM2; C494918:AKT1 protein, human