Akt与肿瘤关系的研究进展_West China Medical Journal

Authors：

黄娜 , 朱静 ,  李为民

Corresponding author：

李为民, Email: huangna213@163.com

Keywords：

Akt; 肿瘤; 研究

Video：

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【摘要】 丝氨酸/苏氨酸蛋白激酶B （protein kinase B， PKB/Akt）作为一种癌基因，通过磷酸化其下游分子，介导或参与细胞周期的调节、细胞生长、凋亡、增殖等多种生物学活性，从而参与肿瘤的发生、发展。这使得Akt可能成为肿瘤基因治疗、抗肿瘤药物开发新的作用靶点。现就Akt的结构、活化和调节及在肿瘤中的作用予以综述。

Citation： 黄娜,朱静,李为民. Akt与肿瘤关系的研究进展. West China Medical Journal, 2010, 25(12): 2291-2294. doi: Copy

1.	Testa JR, Tsichlis PN. Akt signaling in normal and malignant cells[J]. Oncogene, 2005, 24(50): 7391-7393.
2.	Cheng GZ, Park S, Shu S. Advances of Akt pathway in human oncogenesis and as a target for anti-cancer drug discovery[J]. Curr Cancer Drug Targets, 2008, 8(1): 2-6.
3.	Alessi DR, Andjelkovic M, Caudwell B, et al. Mechanism of activation of protein kinase B by insulin and IGF-1[J]. EMBO J, 1996, 15(23): 6541-6551.
4.	Stephens L, Anderson K, Stokoe D, et al. Protein kinase B kinases that mediate phosphatidylinositol 3, 4, 5-triphosphate-dependent activation of protein kinase B[J]. Science, 1998, 279(5351): 710-714.
5.	Williams MR, Arthur JS, Balendran A, et al. The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells[J]. Curr Biol, 2000, 10(8): 439-448.
6.	Tokunaga E, Kimura Y, Oki E, et al. Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone -treated patients[J]. Int J Cancer, 2006, 118(2): 284-289.
7.	Shimizu Y, Segawa T, Inoue T, et al. Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men[J]. BJU Int, 2007, 100(3): 685-690.
8.	Rychahou PG, Kang J, Gulhati P, et al. Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis[J]. Pro Natl Aca Sci USA, 2008, 105(51): 20315-20320.
9.	Weng D, Song X, Xing H, et al. Implication of the Akt2/survivin pathway as a critical target in paclitaxel treatment in human ovarian cancer cells[J]. Cancer Lett, 2009, 273(2): 257-265.
10.	Shah A, Swain WA, Richardson D, et al. Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer[J]. Clin Cancer Res, 2005, 11(8): 2930-2936.
11.	Datta SR, Dudek H, Tao X, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery[J]. Cell, 1997, 91(2): 231-241.
12.	Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival[J]. J Cell Mol Med, 2005, 9(1): 59- 71.
13.	Jeong SJ, Pise-Masison CA, Radonovich MF, et al. Activated Akt regulates NF-kappa B activation, p53 inhibition and cell survival in HTLV-1-transformed cells[J]. Oncogene, 2005, 24 (44): 6719-6728.
14.	Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor[J]. Cell, 1999, 96(6): 857-868.
15.	Diehl JA, Cheng M, Roussel MF, et al. Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization[J]. Genes Dev, 1998, 12(22): 3499-3511.
16.	Graff JR, Konicek BW, McNulty AM, et al. Increased Akt activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27 Kip1 expression[J]. J Biol Chem, 2000, 275(32): 24500-24505.
17.	Dimmeler S, Zeiher AM. Akt takes center stage in angiogenesis signaling[J]. Circ Res, 2000, 86(1): 4-5.
18.	David O, Jett J, LeBeau H, et al. Phospho-Akt overexpression in non-small cell lung cancer confers significant stage-independent survival disadvantage[J]. Clin Cancer Res, 2004, 10(20): 6865-6871.
19.	Massion PP, Taflan PM, Shyr Y, et al. Early involvement of the phosphatidylinositol 3-kinase/Akt pathway in lung cancer progression[J]. Am J Respir Crit Care Med, 2004, 170(10): 1088-1094.
20.	廖永德, 龙庆红, 周晟, 等. 蛋白激酶B在肺鳞癌和腺癌中的表达及其临床病理意义[J]. 中华肿瘤杂志, 2005, 27(3): 156-159.
21.	Shah A, Swain WA, Richardson D, et al. Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer[J]. Clin Cancer Res, 2005, 11(8): 2930-2936.
22.	Tichelaar JW, Zhang Y, leRiche JC, et al. Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies[J]. BMC Cancer, 2005, 5: 155.
23.	Tang JM, He QY, Guo RX, et al. Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis[J]. Lung Cancer, 2006, 51(12): 181-191.
24.	Lim WT, Zhang WH, Miller CR, et al. PTEN and Phosphorylated Akt expression and prognosis in early- and late-stage non-small cell lung cancer[J]. Oncol Rep, 2007, 17(14): 853-857.
25.	Cappuzzo F, Magrini E, Ceresoli GL, et al. Akt phosphorylation and gefitinib efficacy in patients with advanced non-small cell lung cancer[J]. J Natl Cancer Inst, 2004, 96(15): 1133-1141.
26.	Han SW, Kim TY, Jeon Yk, et al. Optimizain of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation , and Akt phosphorylation[J]. Clin Cancer Res, 2006, 12(8): 2538-2544.
27.	Li T, Ling LY, Perez-Soler R. Tumor dependence on the EGFR signaling pathway expressed by the p-EGFR: p-AKT ratio predicts Erlotinib sensitivity in human non-small cell lung cancer (NSCLC) cells expressing wild-type EGFR gene[J]. J Thorac Oncol, 2008, 3(6): 643-647.
28.	余祖滨, 白莉, 张国强, 等. PI3K/Akt 抑制剂对肺癌细胞化疗药物敏感性的影响[J]. 重庆医学, 2009, 38(11): 1340-1342.
29.	Nam SY, Lee HS, Jung GA, et al. Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis[J]. APMIS, 2003, 111(12): 1105-1113.
30.	Roy HK, Olusola BF, Clemens DL, et al. AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis[J]. Carcinogenesis, 2002, 23(1): 201-205.
31.	Zhou X, Tan M, Stone Hawthorne V, et al. Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers[J]. Clin Cancer Res, 2004, 10(20): 6779-6788.
32.	Le Page C, Koumakpayi IH, Alam-Fahmy M, et al. Expression and localisation of Akt-1, Akt-2 and Akt-3 correlate with clinical outcome of prostate cancer patients[J]. Br J Cancer, 2006, 94(12): 1906-1912.
33.	Shtilbans V, Wu M, Burstein DE. Current overview of the role of Akt in cancer studies via applied immunohistochemistry. Ann Diagn Pathol[J], 2008, 12(2): 153-160.
34.	Cicenas J. The potential role of Akt phosphorylation in human cancers[J]. Int J Biol Markers, 2008, 23(1): 1-9.

1. 　Testa JR, Tsichlis PN. Akt signaling in normal and malignant cells[J]. Oncogene, 2005, 24(50): 7391-7393.
2. 　Cheng GZ, Park S, Shu S. Advances of Akt pathway in human oncogenesis and as a target for anti-cancer drug discovery[J]. Curr Cancer Drug Targets, 2008, 8(1): 2-6.
3. 　Alessi DR, Andjelkovic M, Caudwell B, et al. Mechanism of activation of protein kinase B by insulin and IGF-1[J]. EMBO J, 1996, 15(23): 6541-6551.
4. 　Stephens L, Anderson K, Stokoe D, et al. Protein kinase B kinases that mediate phosphatidylinositol 3, 4, 5-triphosphate-dependent activation of protein kinase B[J]. Science, 1998, 279(5351): 710-714.
5. 　Williams MR, Arthur JS, Balendran A, et al. The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells[J]. Curr Biol, 2000, 10(8): 439-448.
6. 　Tokunaga E, Kimura Y, Oki E, et al. Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone -treated patients[J]. Int J Cancer, 2006, 118(2): 284-289.
7. 　Shimizu Y, Segawa T, Inoue T, et al. Increased Akt and phosphorylated Akt expression are associated with malignant biological features of prostate cancer in Japanese men[J]. BJU Int, 2007, 100(3): 685-690.
8. 　Rychahou PG, Kang J, Gulhati P, et al. Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis[J]. Pro Natl Aca Sci USA, 2008, 105(51): 20315-20320.
9. 　Weng D, Song X, Xing H, et al. Implication of the Akt2/survivin pathway as a critical target in paclitaxel treatment in human ovarian cancer cells[J]. Cancer Lett, 2009, 273(2): 257-265.
10. 　Shah A, Swain WA, Richardson D, et al. Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer[J]. Clin Cancer Res, 2005, 11(8): 2930-2936.
11. 　Datta SR, Dudek H, Tao X, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery[J]. Cell, 1997, 91(2): 231-241.
12. 　Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival[J]. J Cell Mol Med, 2005, 9(1): 59- 71.
13. 　Jeong SJ, Pise-Masison CA, Radonovich MF, et al. Activated Akt regulates NF-kappa B activation, p53 inhibition and cell survival in HTLV-1-transformed cells[J]. Oncogene, 2005, 24 (44): 6719-6728.
14. 　Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor[J]. Cell, 1999, 96(6): 857-868.
15. 　Diehl JA, Cheng M, Roussel MF, et al. Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization[J]. Genes Dev, 1998, 12(22): 3499-3511.
16. 　Graff JR, Konicek BW, McNulty AM, et al. Increased Akt activity contributes to prostate cancer progression by dramatically accelerating prostate tumor growth and diminishing p27 Kip1 expression[J]. J Biol Chem, 2000, 275(32): 24500-24505.
17. 　Dimmeler S, Zeiher AM. Akt takes center stage in angiogenesis signaling[J]. Circ Res, 2000, 86(1): 4-5.
18. 　David O, Jett J, LeBeau H, et al. Phospho-Akt overexpression in non-small cell lung cancer confers significant stage-independent survival disadvantage[J]. Clin Cancer Res, 2004, 10(20): 6865-6871.
19. 　Massion PP, Taflan PM, Shyr Y, et al. Early involvement of the phosphatidylinositol 3-kinase/Akt pathway in lung cancer progression[J]. Am J Respir Crit Care Med, 2004, 170(10): 1088-1094.
20. 　廖永德, 龙庆红, 周晟, 等. 蛋白激酶B在肺鳞癌和腺癌中的表达及其临床病理意义[J]. 中华肿瘤杂志, 2005, 27(3): 156-159.
21. 　Shah A, Swain WA, Richardson D, et al. Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer[J]. Clin Cancer Res, 2005, 11(8): 2930-2936.
22. 　Tichelaar JW, Zhang Y, leRiche JC, et al. Increased staining for phospho-Akt, p65/RELA and cIAP-2 in pre-neoplastic human bronchial biopsies[J]. BMC Cancer, 2005, 5: 155.
23. 　Tang JM, He QY, Guo RX, et al. Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis[J]. Lung Cancer, 2006, 51(12): 181-191.
24. 　Lim WT, Zhang WH, Miller CR, et al. PTEN and Phosphorylated Akt expression and prognosis in early- and late-stage non-small cell lung cancer[J]. Oncol Rep, 2007, 17(14): 853-857.
25. 　Cappuzzo F, Magrini E, Ceresoli GL, et al. Akt phosphorylation and gefitinib efficacy in patients with advanced non-small cell lung cancer[J]. J Natl Cancer Inst, 2004, 96(15): 1133-1141.
26. 　Han SW, Kim TY, Jeon Yk, et al. Optimizain of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation , and Akt phosphorylation[J]. Clin Cancer Res, 2006, 12(8): 2538-2544.
27. 　Li T, Ling LY, Perez-Soler R. Tumor dependence on the EGFR signaling pathway expressed by the p-EGFR: p-AKT ratio predicts Erlotinib sensitivity in human non-small cell lung cancer (NSCLC) cells expressing wild-type EGFR gene[J]. J Thorac Oncol, 2008, 3(6): 643-647.
28. 　余祖滨, 白莉, 张国强, 等. PI3K/Akt 抑制剂对肺癌细胞化疗药物敏感性的影响[J]. 重庆医学, 2009, 38(11): 1340-1342.
29. 　Nam SY, Lee HS, Jung GA, et al. Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis[J]. APMIS, 2003, 111(12): 1105-1113.
30. 　Roy HK, Olusola BF, Clemens DL, et al. AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis[J]. Carcinogenesis, 2002, 23(1): 201-205.
31. 　Zhou X, Tan M, Stone Hawthorne V, et al. Activation of the Akt/mammalian target of rapamycin/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers[J]. Clin Cancer Res, 2004, 10(20): 6779-6788.
32. 　Le Page C, Koumakpayi IH, Alam-Fahmy M, et al. Expression and localisation of Akt-1, Akt-2 and Akt-3 correlate with clinical outcome of prostate cancer patients[J]. Br J Cancer, 2006, 94(12): 1906-1912.
33. 　Shtilbans V, Wu M, Burstein DE. Current overview of the role of Akt in cancer studies via applied immunohistochemistry. Ann Diagn Pathol[J], 2008, 12(2): 153-160.
34. 　Cicenas J. The potential role of Akt phosphorylation in human cancers[J]. Int J Biol Markers, 2008, 23(1): 1-9.

West China Medical Journal

Akt与肿瘤关系的研究进展

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