Low expression of Beclin 1 and elevated expression of HIF-1α refine distant metastasis risk and predict poor prognosis of ER-positive, HER2-negative breast cancer

Medical Oncology

Volumn 30, Issue 1, 2013, Pages

  Dong, Min ^a   Wan, Xiang Bo ^a   Yuan, Zhong Yu ^b   Wei, Li ^a   Fan, Xin Juan ^a   Wang, Tian Tian ^a   Lv, Yan Chun ^b   Li, Xing ^a   Chen, Zhan Hong ^a   Chen, Jie ^a   Lin, Qu ^a   Wen, Jing Yun ^a   Ma, Xiao Kun ^a   Liu, Quentin ^a,b,c   Wu, Xiang Yuan ^a  

^a SUN YAT SEN UNIVERSITY   (China)

^b SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

^c DALIAN MEDICAL UNIVERSITY   (China)

Author keywords

Autophagy; Beclin 1; Breast cancer; HIF 1 ; Prognosis

Indexed keywords

AROMATASE INHIBITOR; BECLIN 1; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ESTROGEN RECEPTOR; FLUOROURACIL; HYPOXIA INDUCIBLE FACTOR 1ALPHA; PACLITAXEL; TAMOXIFEN; APOPTOSIS REGULATORY PROTEIN; BECN1 PROTEIN, HUMAN; ERBB2 PROTEIN, HUMAN; HIF1A PROTEIN, HUMAN; MEMBRANE PROTEIN; TUMOR MARKER;

ADULT; AGED; ARTICLE; BREAST ADENOCARCINOMA; BREAST CANCER; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER RISK; DISTANT METASTASIS; DISTANT METASTASIS FREE SURVIVAL; FEMALE; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LYMPH NODE DISSECTION; LYMPH NODE METASTASIS; MAJOR CLINICAL STUDY; MALE; MASTECTOMY; MULTIPLE CYCLE TREATMENT; OVERALL SURVIVAL; PARTIAL MASTECTOMY; PRIORITY JOURNAL; PROTEIN EXPRESSION; TISSUE MICROARRAY; ADENOCARCINOMA; BREAST TUMOR; METABOLISM; MIDDLE AGED; MORTALITY; MULTIVARIATE ANALYSIS; PATHOLOGY; PREDICTIVE VALUE; PROGNOSIS; PROPORTIONAL HAZARDS MODEL; SURVIVAL; VERY ELDERLY;

ADENOCARCINOMA; ADULT; AGED; AGED, 80 AND OVER; APOPTOSIS REGULATORY PROTEINS; BREAST NEOPLASMS; FEMALE; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MEMBRANE PROTEINS; MIDDLE AGED; MULTIVARIATE ANALYSIS; PREDICTIVE VALUE OF TESTS; PROGNOSIS; PROPORTIONAL HAZARDS MODELS; RECEPTOR, ERBB-2; SURVIVAL ANALYSIS; TUMOR MARKERS, BIOLOGICAL;

EID: 84873699941     PISSN: 13570560     EISSN: 1559131X     Source Type: Journal    
DOI: 10.1007/s12032-012-0355-0     Document Type: Article

References (53)

1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212-36. doi: 10.3322/caac.20121.
2. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98(19):10869-74. doi: 10.1073/pnas.19136709898/19/10869.
3. Lowery AJ, Kell MR, Glynn RW, Kerin MJ, Sweeney KJ. Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat. 2012;133(3):831-41. doi: 10.1007/s10549-011-1891-6.
4. Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncol. 2011;12(12):1101-8. doi: 10.1016/S1470-2045(11)70270-4.
5. Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, et al. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008;9(1):23-8. doi: 10.1016/S1470-2045(07) 70386-8.
6. Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101(10):736-50. doi: 10.1093/jnci/djp082.
7. Mehta RJ, Jain RK, Leung S, Choo J, Nielsen T, Huntsman D, et al. FOXA1 is an independent prognostic marker for ER-positive breast cancer. Breast Cancer Res Treat. 2012;131(3):881-90. doi: 10.1007/s10549-011-1482-6.
8. Mehra R, Varambally S, Ding L, Shen R, Sabel MS, Ghosh D, et al. Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis. Cancer Res. 2005;65(24):11259-64. doi: 10.1158/0008-5472.CAN-05-2495.
9. Davies MP, Barraclough DL, Stewart C, Joyce KA, Eccles RM, Barraclough R, et al. Expression and splicing of the unfolded protein response gene XBP-1 are significantly associated with clinical outcome of endocrine-treated breast cancer. Int J Cancer. 2008;123(1):85-8. doi: 10.1002/ijc.23479.
10. Hugh J, Hanson J, Cheang MC, Nielsen TO, Perou CM, Dumontet C, et al. Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol. 2009;27(8):1168-76. doi: 10.1200/JCO.2008.18.1024.
11. Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004;6(4):463-77. doi: S1534580704000991.
12. Morselli E, Galluzzi L, Kepp O, Vicencio JM, Criollo A, Maiuri MC, et al. Anti- and pro-tumor functions of autophagy. Biochim Biophys Acta. 2009;1793(9):1524-32. doi: 10.1016/j.bbamcr.2009.01.006.
13. White E, Karp C, Strohecker AM, Guo Y, Mathew R. Role of autophagy in suppression of inflammation and cancer. Curr Opin Cell Biol. 2010;22(2):212-7. doi: 10.1016/j.ceb.2009.12.008.
14. Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res. 2005;8(1):3-5. doi: 10.1089/rej.2005.8.3.
15. Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, Wesley JB, et al. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem. 2008;283(16):10892-903. doi: 10.1074/jbc.M800102200.
16. O'Donovan TR, O'Sullivan GC, McKenna SL. Induction of autophagy by drug-resistant esophageal cancer cells promotes their survival and recovery following treatment with chemotherapeutics. Autophagy. 2011;7(5):509-24.
17. Furuya N, Yu J, Byfield M, Pattingre S, Levine B. The evolutionarily conserved domain of Beclin 1 is required for Vps34 binding, autophagy and tumor suppressor function. Autophagy. 2005;1(1):46-52.
18. Takahashi Y, Coppola D, Matsushita N, Cualing HD, Sun M, Sato Y, et al. Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis. Nat Cell Biol. 2007;9(10):1142-51. doi: 10.1038/ncb1634.
19. Li DD, Wang LL, Deng R, Tang J, Shen Y, Guo JF, et al. The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cells. Oncogene. 2009;28(6):886-98. doi: 10.1038/onc.2008.441.
20. Pattingre S, Espert L, Biard-Piechaczyk M, Codogno P. Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie. 2008;90(2):313-23. doi: 10.1016/j.biochi.2007.08.014.
21. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 2005;122(6):927-39. doi: 10.1016/j.cell.2005.07.002.
22. Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB, et al. Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004;6(12):1221-8. doi: 10.1038/ncb1192.
23. Fimia GM, Stoykova A, Romagnoli A, Giunta L, Di Bartolomeo S, Nardacci R, et al. Ambra1 regulates autophagy and development of the nervous system. Nature. 2007;447(7148):1121-5. doi: 10.1038/nature05925.
24. Itakura E, Kishi C, Inoue K, Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol Biol Cell. 2008;19(12):5360-72. doi: 10.1091/mbc.E08-01-0080.
25. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402(6762):672-6. doi: 10.1038/45257.
26. Yao Q, Chen J, Lv Y, Wang T, Zhang J, Fan J, et al. The significance of expression of autophagy-related gene Beclin, Bcl-2, and Bax in breast cancer tissues. Tumour Biol. 2011;32(6):1163-71. doi: 10.1007/s13277-011-0219-9.
27. Pirtoli L, Cevenini G, Tini P, Vannini M, Oliveri G, Marsili S, et al. The prognostic role of Beclin 1 protein expression in high-grade gliomas. Autophagy. 2009;5(7):930-6.
28. Wan XB, Fan XJ, Chen MY, Xiang J, Huang PY, Guo L, et al. Elevated Beclin 1 expression is correlated with HIF-1alpha in predicting poor prognosis of nasopharyngeal carcinoma. Autophagy. 2010;6(3):395-404.
29. Shi YH, Ding ZB, Zhou J, Qiu SJ, Fan J. Prognostic significance of Beclin 1-dependent apoptotic activity in hepatocellular carcinoma. Autophagy. 2009;5(3):380-2.
30. Chen Y, Lu Y, Lu C, Zhang L. Beclin-1 expression is a predictor of clinical outcome in patients with esophageal squamous cell carcinoma and correlated to hypoxia-inducible factor (HIF)-1alpha expression. Pathol Oncol Res. 2009;15(3):487-93. doi: 10.1007/s12253-008-9143-8.
31. Li BX, Li CY, Peng RQ, Wu XJ, Wang HY, Wan DS, et al. The expression of beclin 1 is associated with favorable prognosis in stage IIIB colon cancers. Autophagy. 2009;5(3):303-6.
32. Giatromanolaki A, Koukourakis MI, Koutsopoulos A, Chloropoulou P, Liberis V, Sivridis E. High Beclin 1 expression defines a poor prognosis in endometrial adenocarcinomas. Gynecol Oncol. 2011;123(1):147-51. doi: 10.1016/j.ygyno.2011. 06.023.
33. Dong LW, Hou YJ, Tan YX, Tang L, Pan YF, Wang M, et al. Prognostic significance of Beclin 1 in intrahepatic cholangiocellular carcinoma. Autophagy. 2011;7(10):1222-9. doi: 10.4161/auto.7.10.16610.
34. Huang JJ, Li HR, Huang Y, Jiang WQ, Xu RH, Huang HQ, et al. Beclin 1 expression: a predictor of prognosis in patients with extranodal natural killer T-cell lymphoma, nasal type. Autophagy. 2010;6(6):777-83.
35. Huang JJ, Zhu YJ, Lin TY, Jiang WQ, Huang HQ, Li ZM. Beclin 1 expression predicts favorable clinical outcome in patients with diffuse large B-cell lymphoma treated with R-CHOP. Hum Pathol. 2011;42(10):1459-66. doi: 10.1016/j.humpath.2010.12.014.
36. Ding ZB, Shi YH, Zhou J, Qiu SJ, Xu Y, Dai Z, et al. Association of autophagy defect with a malignant phenotype and poor prognosis of hepatocellular carcinoma. Cancer Res. 2008;68(22):9167-75. doi: 10.1158/0008-5472.CAN-08-1573.
37. Crazzolara R, Bradstock KF, Bendall LJ. RAD001 (Everolimus) induces autophagy in acute lymphoblastic leukemia. Autophagy. 2009;5(5):727-8.
38. Lin CI, Whang EE, Donner DB, Du J, Lorch J, He F, et al. Autophagy induction with RAD001 enhances chemosensitivity and radiosensitivity through Met inhibition in papillary thyroid cancer. Mol Cancer Res. 2010;8(9):1217-26. doi: 10.1158/1541-7786.MCR-10-0162.
39. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403-10.
40. Koukourakis MI, Giatromanolaki A, Sivridis E, Pitiakoudis M, Gatter KC, Harris AL. Beclin 1 over- and underexpression in colorectal cancer: distinct patterns relate to prognosis and tumour hypoxia. Br J Cancer. 2010;103(8):1209-14. doi: 10.1038/sj.bjc.6605904.
41. Shen Y, Li DD, Wang LL, Deng R, Zhu XF. Decreased expression of autophagy-related proteins in malignant epithelial ovarian cancer. Autophagy. 2008;4(8):1067-8.
42. Jiang ZF, Shao LJ, Wang WM, Yan XB, Liu RY. Decreased expression of Beclin-1 and LC3 in human lung cancer. Mol Biol Rep. 2012;39(1):259-67. doi: 10.1007/s11033-011-0734-1.
43. Won KY, Kim GY, Lim SJ, Kim YW. Decreased Beclin-1 expression is correlated with the growth of the primary tumor in patients with squamous cell carcinoma and adenocarcinoma of the lung. Hum Pathol. 2012;43(1):62-8. doi: 10.1016/j.humpath.2011.04.007.
44. Kim HS, Lee SH, Do SI, Lim SJ, Park YK, Kim YW. Clinicopathologic correlation of beclin-1 expression in pancreatic ductal adenocarcinoma. Pathol Res Pract. 2011;207(4):247-52. doi: 10.1016/j.prp.2011.02.007.
45. Won KY, Kim GY, Kim YW, Song JY, Lim SJ. Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast cancer. Hum Pathol. 2010;41(1):107-12. doi: 10.1016/j.humpath.2009.07.006.
46. Vazquez-Martin A, Cufi S, Oliveras-Ferraros C, Martin-Castillo B, Del Barco S, Lopez-Bonet E, et al. Expression status of the autophagy-regulatory gene ATG6/BECN1 in ERBB2-positive breast carcinomas: bypassing ERBB2-induced oncogenic senescence to regulate the efficacy of ERBB2-targeted therapies. Genes Chromosomes Cancer. 2011;50(4):284-90. doi: 10.1002/gcc.20846.
47. Mathew R, Kongara S, Beaudoin B, Karp CM, Bray K, Degenhardt K, et al. Autophagy suppresses tumor progression by limiting chromosomal instability. Genes Dev. 2007;21(11):1367-81. doi: 10.1101/gad.1545107.
48. Karantza-Wadsworth V, Patel S, Kravchuk O, Chen G, Mathew R, Jin S, et al. Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 2007;21(13):1621-35. doi: 10.1101/gad.1565707.
49. Wang Y, Yin Q, Yu Q, Zhang J, Liu Z, Wang S, et al. A retrospective study of breast cancer subtypes: the risk of relapse and the relations with treatments. Breast Cancer Res Treat. 2011;130(2):489-98. doi: 10.1007/s10549-011-1709-6.
50. Li X, Fan Z. The epidermal growth factor receptor antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1alpha and Bcl-2 and activating the beclin 1/hVps34 complex. Cancer Res. 2010;70(14):5942-52. doi: 10.1158/0008-5472.CAN-10-0157.
51. Schindl M, Schoppmann SF, Samonigg H, Hausmaninger H, Kwasny W, Gnant M, et al. Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin Cancer Res. 2002;8(6):1831-7.
52. Bos R, van der Groep P, Greijer AE, Shvarts A, Meijer S, Pinedo HM, et al. Levels of hypoxia-inducible factor-1alpha independently predict prognosis in patients with lymph node negative breast carcinoma. Cancer. 2003;97(6):1573-81. doi: 10.1002/cncr.11246.
53. Gruber G, Greiner RH, Hlushchuk R, Aebersold DM, Altermatt HJ, Berclaz G, et al. Hypoxia-inducible factor 1 alpha in high-risk breast cancer: an independent prognostic parameter? Breast Cancer Res. 2004;6(3):R191-8. doi: 10.1186/bcr775bcr775.