Histological evaluation of AMPK signalling in primary breast cancer.
Histological evaluation of AMPK signalling in primary breast cancer.
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DOI：
10.1186/1471-2407-9-307
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发表时间：
2009-09-01
期刊：
影响因子：
3.8
通讯作者：
Thompson AM
中科院分区：
文献类型：
--
作者：
Hadad SM;Baker L;Quinlan PR;Robertson KE;Bray SE;Thomson G;Kellock D;Jordan LB;Purdie CA;Hardie DG;Fleming S;Thompson AM
AMP活化蛋白激酶（AMPK）作为细胞燃料计量器，通过抑制细胞生长和生物合成过程来响应能量应激，从而确保只有在有足够的代谢资源的情况下才能进行能量消耗过程。AMPK通路的功能障碍可能使癌细胞经历不受控制的增殖，而不管它们的分子能量水平如何。本研究的目的是研究AMPK磷酸化状态在原发性乳腺癌组织学与临床和病理参数的关系。使用磷酸化AMPK（pAMPK）、磷酸化乙酰辅酶A羧化酶（pACC）（AMPK、HER 2、ERα和Ki 67的既定靶点）的抗体，在117例和237例原发性乳腺癌的两个队列的组织微阵列（TMA）载玻片上进行免疫组织化学。采用快速评分法进行评分，并将蛋白表达模式与临床和病理数据进行比较，包括至少5年的随访。与正常乳腺上皮中的强表达相比，使用pAMPK抗体在两个患者队列的101/113（89.4%）和217/236（91.9%）中证实了信号降低。pACC与pAMPK表达显著相关（分别为p = 0.007和p = 0.014）。对于两个组群，pAMPK信号降低与较高的组织学分级（分别为p = 0.010和p = 0.021）和腋窝淋巴结转移（分别为p = 0.061和p = 0.039）显著相关。pAMPK与HER 2、ERα或Ki 67表达、无病生存期或总生存期之间均无显著相关性。本研究通过免疫组织化学扩展了体外证据，以证实AMPK在原发性乳腺癌中功能障碍。通过AMPK途径的信号传导减少，与组织学分级和腋窝淋巴结转移呈负相关，表明AMPK再激活可能在乳腺癌中具有治疗潜力。
AMP-activated protein kinase (AMPK) acts as a cellular fuel gauge that responds to energy stress by suppressing cell growth and biosynthetic processes, thus ensuring that energy-consuming processes proceed only if there are sufficient metabolic resources. Malfunction of the AMPK pathway may allow cancer cells to undergo uncontrolled proliferation irrespective of their molecular energy levels. The aim of this study was to examine the state of AMPK phosphorylation histologically in primary breast cancer in relation to clinical and pathological parameters. Immunohistochemistry was performed using antibodies to phospho-AMPK (pAMPK), phospho-Acetyl Co-A Carboxylase (pACC) an established target for AMPK, HER2, ERα, and Ki67 on Tissue Micro-Array (TMA) slides of two cohorts of 117 and 237 primary breast cancers. The quick score method was used for scoring and patterns of protein expression were compared with clinical and pathological data, including a minimum 5 years follow up. Reduced signal, compared with the strong expression in normal breast epithelium, using a pAMPK antibody was demonstrated in 101/113 (89.4%) and 217/236 (91.9%) of two cohorts of patients. pACC was significantly associated with pAMPK expression (p = 0.007 & p = 0.014 respectively). For both cohorts, reduced pAMPK signal was significantly associated with higher histological grade (p = 0.010 & p = 0.021 respectively) and axillary node metastasis (p = 0.061 & p = 0.039 respectively). No significant association was found between pAMPK and any of HER2, ERα, or Ki67 expression, disease-free survival or overall survival. This study extends in vitro evidence through immunohistochemistry to confirm that AMPK is dysfunctional in primary breast cancer. Reduced signalling via the AMPK pathway, and the inverse relationship with histological grade and axillary node metastasis, suggests that AMPK re-activation could have therapeutic potential in breast cancer.
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影响因子：
--
作者：
Hawley SA;Boudeau J;Reid JL;Mustard KJ;Udd L;Mäkelä TP;Alessi DR;Hardie DG
通讯作者：
Hardie DG
影响因子：
2.1
作者：
Kimura, N;Tokunaga, C;Yonezawa, K
通讯作者：
Yonezawa, K
DOI：
10.1006/bbrc.2001.5627
发表时间：
2001-09-21
影响因子：
3.1
作者：
Imamura, K;Ogura, T;Esumi, H
通讯作者：
Esumi, H
影响因子：
9.2
作者：
Horman, S;Browne, GJ;Rider, MH
通讯作者：
Rider, MH
DOI：
10.1074/jbc.m706536200
发表时间：
2007-11-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Göransson O;McBride A;Hawley SA;Ross FA;Shpiro N;Foretz M;Viollet B;Hardie DG;Sakamoto K
通讯作者：
Sakamoto K