Stål Olle, Pérez-Tenorio Gizeh, Akerberg Linda, Olsson Birgit, Nordenskjöld Bo, Skoog Lambert, Rutqvist Lars Erik
Department of Biomedicine and Surgery, Division of Oncology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Breast Cancer Res. 2003;5(2):R37-44. doi: 10.1186/bcr569. Epub 2003 Jan 20.
The 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.
We 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.
Marked 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).
Activation 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.
丝氨酸/苏氨酸激酶Akt，即蛋白激酶B，因其抑制细胞凋亡的活性，最近成为人们关注的焦点。它作为生长因子受体信号的转导分子发挥作用，这些受体可激活磷脂酰肌醇3激酶，从而介导细胞存活。
我们采用免疫组织化学方法分析了280例绝经后患者冷冻肿瘤样本中Akt1和Akt2亚型以及磷酸化Akt（pAkt）的表达情况。这些患者参与了一项随机试验，比较环磷酰胺-甲氨蝶呤-5-氟尿嘧啶化疗与术后放疗。患者同时被随机分为接受他莫昔芬治疗或不接受内分泌治疗。
24%的肿瘤中Akt1呈明显染色，但Akt2仅为4%。在另外26%的肿瘤中观察到Akt2阳性细胞的频率较低（1%-10%）。pAkt与Akt1和Akt2的表达均显著相关。erbB2的过表达与pAkt显著相关（P = 0.0028）。在雌激素受体（ER）阳性患者中分析了他莫昔芬的益处。Akt阴性（Akt1、Akt2或pAkt无过表达）的患者从他莫昔芬治疗中显示出显著益处。对于ER+/Akt1-患者，接受与未接受他莫昔芬治疗的远处复发相对率为0.44（95%置信区间[CI]，0.25 - 0.79），而对于ER+/Akt1+患者，该相对率为0.72（95%CI，0.
