Abstract
Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) was reported to be implicated in various cellular processes and involved in control of cell cycle regulation and transcription. It may play a critical role in oncogenesis. In this study, to investigate the potential roles of SGTA in breast cancer, expression patterns, interaction and the correlation with clinical/prognostic factors of SGTA and Ki-67 were examined among patients with breast cancer. Immunohistochemistry and Western blot analysis were performed for SGTA in 100 breast carcinoma samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine the prognostic significance. We found that SGTA was overexpressed in breast carcinoma compared with the adjacent normal tissues. High expression of SGTA was positively associated with histological grade (P = 0.002) and Ki-67 (P = 0.001). Univariate analysis showed that SGTA expression was associated with a poor prognosis (P = 0.002). Kaplan–Meier survival curves of the study population showed that high expression level of SGTA significantly correlated with short-term survival. While in vitro, SGTA depletion by small interfering RNA inhibited cell proliferation and cell cycle in breast cancer cell lines. Western blot analyses showed that SGTA depletion decreased cyclin A, cyclin B and CDK2, whereas increased p27 levels. Additionally, treatment of phosphatidylinositol 3-kinase inhibitor LY294002 could arrest cells growth and diminish SGTA expression. These results suggested that SGTA overexpression was involved in the pathogenesis of breast cancer which might serve as a future target for novel treatment in breast cancer.
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References
Angeletti PC, Walker D, Panganiban AT (2002) Small glutamine-rich protein/viral protein U-binding protein is a novel cochaperone that affects heat shock protein 70 activity. Cell Stress Chaperones 7(3):258–268
Buchanan G, Ricciardelli C, Harris JM, Prescott J, Yu ZC, Jia L, Butler LM, Marshall VR, Scher HI, Gerald WL, Coetzee GA, Tilley WD (2007) Control of androgen receptor signaling in prostate cancer by the cochaperone small glutamine rich tetratricopeptide repeat containing protein alpha. Cancer Res 67(20):10087–10096. doi:10.1158/0008-5472.CAN-07-1646
Chiarle R, Pagano M, Inghirami G (2001) The cyclin dependent kinase inhibitor p27 and its prognostic role in breast cancer. Breast Cancer Res 3(2):91–94
Cziepluch C, Kordes E, Poirey R, Grewenig A, Rommelaere J, Jauniaux JC (1998) Identification of a novel cellular TPR-containing protein, SGT, that interacts with the nonstructural protein NS1 of parvovirus H-1. J Virol 72(5):4149–4156
Cziepluch C, Lampel S, Grewenig A, Grund C, Lichter P, Rommelaere J (2000) H-1 parvovirus-associated replication bodies: a distinct virus-induced nuclear structure. J Virol 74(10):4807–4815
D’Andrea LD, Regan L (2003) TPR proteins: the versatile helix. Trends Biochem Sci 28(12):655–662. doi:10.1016/j.tibs.2003.10.007
Eroles P, Bosch A, Perez-Fidalgo JA, Lluch A (2012) Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. Cancer Treat Rev 38(6):698–707. doi:10.1016/j.ctrv.11.005
Fonte V, Kapulkin WJ, Taft A, Fluet A, Friedman D, Link CD (2002) Interaction of intracellular beta amyloid peptide with chaperone proteins. Proc Natl Acad Sci USA 99(14):9439–9444. doi:10.1073/pnas.152313999
Kelloff GJ, Sigman CC (2012) Cancer biomarkers: selecting the right drug for the right patient. Nat Rev Drug Discov 11(3):201–214. doi:10.1038/nrd3651
Lu C, Liu G, Cui X, Zhang J, Wei L, Wang Y, Yang X, Liu Y, Cong X, Lv L, Ni R, Huang X (2014) Expression of SGTA correlates with prognosis and tumor cell proliferation in human hepatocellular carcinoma. Pathol Oncol Res 20(1):51–60. doi:10.1007/s12253-013-9657-6
Mann CD, Neal CP, Garcea G, Manson MM, Dennison AR, Berry DP (2007) Prognostic molecular markers in hepatocellular carcinoma: a systematic review. Eur J Cancer 43(6):979–992. doi:10.1016/j.ejca.2007.01.004
Moritz A, Li Y, Guo A, Villen J, Wang Y, MacNeill J, Kornhauser J, Sprott K, Zhou J, Possemato A, Ren JM, Hornbeck P, Cantley LC, Gygi SP, Rush J, Comb MJ (2010) Akt-RSK-S6 kinase signaling networks activated by oncogenic receptor tyrosine kinases. Sci Signal 3(136):ra64. doi:10.1126/scisignal.2000998
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108
Plas DR, Thompson CB (2003) Akt activation promotes degradation of tuberin and FOXO3a via the proteasome. J Biol Chem 278(14):12361–12366. doi:10.1074/jbc.M213069200
Schantl JA, Roza M, De Jong AP, Strous GJ (2003) Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor. Biochem J 373(Pt 3):855–863. doi:10.1042/BJ20021591
Trotta AP, Need EF, Selth LA, Chopra S, Pinnock CB, Leach DA, Coetzee GA, Butler LM, Tilley WD, Buchanan G (2013) Knockdown of the cochaperone SGTA results in the suppression of androgen and PI3K/Akt signaling and inhibition of prostate cancer cell proliferation. Int J Cancer 133(12):2812–2823. doi:10.1002/ijc.28310
Unek G, Ozmen A, Mendilcioglu I, Simsek M, Korgun ET (2014) Immunohistochemical distribution of cell cycle proteins p27, p57, cyclin D3, PCNA and Ki67 in normal and diabetic human placentas. J Mol Histol 45(1):21–34. doi:10.1007/s10735-013-9534-3
Wang H, Zhang Q, Zhu D (2003) hSGT interacts with the N-terminal region of myostatin. Biochem Biophys Res Commun 311(4):877–883. doi:10.1016/j.bbrc.2003.10.080
Wang H, Shen H, Wang Y, Li Z, Yin H, Zong H, Jiang J, Gu J (2005) Overexpression of small glutamine-rich TPR-containing protein promotes apoptosis in 7721 cells. FEBS Lett 579(5):1279–1284. doi:10.1016/j.febslet.2004.12.092
Wilson CM, Tobin S, Young RC (2004) The exploding worldwide cancer burden: the impact of cancer on women. Int J Gynecol Cancer 14(1):1–11
Winnefeld M, Rommelaere J, Cziepluch C (2004) The human small glutamine-rich TPR-containing protein is required for progress through cell division. Exp Cell Res 293(1):43–57. doi:10.1016/j.yexcr.2003.09.028
Winnefeld M, Grewenig A, Schnolzer M, Spring H, Knoch TA, Gan EC, Rommelaere J, Cziepluch C (2006) Human SGT interacts with Bag-6/Bat-3/Scythe and cells with reduced levels of either protein display persistence of few misaligned chromosomes and mitotic arrest. Exp Cell Res 312(13):2500–2514. doi:10.1016/j.yexcr.2006.04.020
Xue Q, Lv L, Wan C, Chen B, Li M, Ni T, Liu Y, Cong X, Zhou Y, Ni R, Mao G (2013) Expression and clinical role of small glutamine-rich tetratricopeptide repeat (TPR)-containing protein alpha (SGTA) as a novel cell cycle protein in NSCLC. J Cancer Res Clin Oncol 139(9):1539–1549. doi:10.1007/s00432-013-1474-5
Yang X, Cheng L, Li M, Shi H, Ren H, Ding Z, Liu F, Wang Y, Cheng C (2014) High expression of SGTA in esophageal squamous cell carcinoma correlates with proliferation and poor prognosis. J Cell Biochem 115(1):141–150. doi:10.1002/jcb.24641
Yin H, Wang H, Zong H, Chen X, Wang Y, Yun X, Wu Y, Wang J, Gu J (2006) SGT, a Hsp90beta binding partner, is accumulated in the nucleus during cell apoptosis. Biochem Biophys Res Commun 343(4):1153–1158. doi:10.1016/j.bbrc.2006.03.090
Acknowledgments
Special thanks to Yan Wu (Department of Pathology, The People’s Hospital of Taixing City) for helping with the statistical analysis. Furthermore, I would like to thank Longjin He for help and encouragement.
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The authors declare that they have no conflict of interests.
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Ting Zhu and Zhengxiang Ji have contributed equally to this work.
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Zhu, T., Ji, Z., Xu, C. et al. Expression and prognostic role of SGTA in human breast carcinoma correlates with tumor cell proliferation. J Mol Hist 45, 665–677 (2014). https://doi.org/10.1007/s10735-014-9586-z
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DOI: https://doi.org/10.1007/s10735-014-9586-z