期刊论文详细信息
BMC Cancer
Over-expressions of AMPK subunits in ovarian carcinomas with significant clinical implications
Cuilan Li1  Vincent WS Liu2  Pui M Chiu1  David W Chan1  Hextan YS Ngan2 
[1] Department of Obstetrics and Gynecology, LKS Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong SAR, People’s Republic of China
[2] Department of Obstetrics and Gynecology, Queen Mary Hospital, 6th Floor, Professorial Block, Pokfulam, Hong Kong SAR, People’s Republic of China
关键词: Ovarian carcinoma;    Differential gene expression;    AMPK subunits;    AMPK;   
Others  :  1080251
DOI  :  10.1186/1471-2407-12-357
 received in 2011-09-14, accepted in 2012-07-16,  发布年份 2012
PDF
【 摘 要 】

Background

AMP-activated protein kinase (AMPK) has recently been considered as a potential target for cancer therapy. However, the expression status of various subunits of the heterotrimeric AMPK in human cancers is rarely reported. We decided to determine their expressions in ovarian carcinomas and their relationships with the disease.

Methods

Expressions and locations of the AMPK-α1, -α2, -β1, -β2, -γ1 and -γ2 were detected by quantitative PCR (Q-PCR) and immunohistochemical staining (IHC). Their expression levels in ovarian tumors were compared with normal controls and also correlated with clinicopathological parameters.

Results

Except AMPK-α1, expressions of the other five AMPK subunits are significantly higher in ovarian carcinomas as determined by Q-PCR. Although IHC detection of AMPK-γ1 and -γ2 were not successful, over-expressions of AMPK-α2, -β1, and -β2 were further confirmed by IHC. Over-expressions of various AMPK subunits occurred independently and were mainly detected in the cytoplasm. Interestingly, AMPK-α2 and -β1 were also detected in the nucleus and cell membrane, respectively. Clinical correlation analyses indicate that expressions of different AMPK subunits are associated with different subtypes of carcinoma. High expression of AMPK-α2 is significantly associated with endometrioid carcinomas. On the other hand, high expressions of AMPK-β and subunits are associated with mucinous and serous carcinomas, respectively. Furthermore, high expressions of AMPK-β1 and -γ2 are also associated with early and late stages of disease, respectively. Finally, patients with high expression of AMPK-α2 had better prognosis.

Conclusions

Aberrant expressions of AMPK subunits may play important roles in ovarian carcinogenesis. Each AMPK subunit may have its own function other than just a component of the AMPK molecule. Correlations with clinical parameters suggest that expressions of AMPK subunits have different clinical implications in ovarian cancer development.

【 授权许可】

   
2012 Li et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20141202234123611.pdf 2605KB PDF download
Figure 5. 72KB Image download
Figure 4. 100KB Image download
Figure 3. 139KB Image download
Figure 2. 196KB Image download
Figure 1. 46KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】
  • [1]Hardie DG: AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 2007, 8:774-785.
  • [2]Steinberg GR, Kemp BE: AMPK in Health and Disease. Physiol Rev 2009, 89:1025-1078.
  • [3]Shackelford DB, Shaw RJ: The LKB1–AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer 2009, 9:563-575.
  • [4]Fogarty S, Hardie DG: Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim Biophys Acta 2010, 1804:581-591.
  • [5]Yu SY, Chan DW, Liu VW, Ngan HY: Inhibition of cervical cancer cell growth through activation of upstream kinases of AMP-activated protein kinase. Tumour Biol 2009, 30:80-85.
  • [6]Gotlieb WH, Saumet J, Beauchamp MC, Gu J, Lau S, Pollak MN, Bruchim I: In vitro metformin anti-neoplastic activity in epithelial ovarian cancer. Gynecol Oncol 2008, 110:246-250.
  • [7]Rattan R, Giri S, Hartmann LC, Shridhar V: Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner. J Cell Mol Med 2011, 15:166-178.
  • [8]Yasmeen A, Beauchamp MC, Piura E, Segal E, Pollak M, Gotlieb WH: Induction of apoptosis by metformin in epithelial ovarian cancer: Involvement of the Bcl-2 family proteins. Gynecol Oncol 2011, 121:492-498.
  • [9]Brenman JE: AMPK/LKB1 signaling in epithelial cell polarity and cell division. Cell Cycle 2007, 6:2755-2759.
  • [10]Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008, 3:1101-1108.
  • [11]Huang FY, Chiu PM, Tam KF, Kwok YK, Lau ET, Tang MH, Ng TY, Liu VW, Cheung AN, Ngan HY: Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a potential candidate cancer gene of cervical cancer. Gynecol Oncol 2006, 103:219-225.
  • [12]Wang Y, Chan DW, Liu VW, Chiu PM, Ngan HY: Differential functions of growth factor receptor-bound protein 7 (GRB7) and its variant GRB7v in ovarian carcinogenesis. Clin Cancer Res 2010, 16:2529-2539.
  • [13]Hallstrom TC, Mori S, Nevins JR: An E2F1-dependent gene expression program that determines the balance between proliferation and cell death. Cancer Cell 2008, 13:11-22.
  • [14]Neurath KM, Keough MP, Mikkelsen T, Claffey KP: AMP-dependent protein kinase alpha 2 isoform promotes hypoxia-induced VEGF expression in human glioblastoma. Glia 2006, 53:733-743.
  • [15]Lee YG, Lee SW, Sin HS, Kim EJ, Um SJ: Kinase activity-independent suppression of p73alpha by AMP-activated kinase alpha (AMPKalpha). Oncogene 2009, 28:1040-1052.
  • [16]Li J, Jiang P, Robinson M, Lawrence TS, Sun Y: AMPK-beta1 subunit is a p53-independent stress responsive protein that inhibits tumor cell growth upon forced expression. Carcinogenesis 2003, 24:827-834.
  文献评价指标  
  下载次数:49次 浏览次数:20次