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Expression of PR-SET7 in esophageal carcinoma and its correlation with clinical features and PCNA index |
ZHENG Jian,MA Shikun,and CHEN Jian |
Department of Surgery,Jiangsu Provincial Corps Hospital of Chinese People’s Armed Police Force,Yangzhou 225003,China |
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Abstract Objective To investigate the expression of lysine methyltransferase(KMT) PR-SET7 in esophageal carcinoma and its relationship with clinical features and proliferating cell nuclear antigen(PCNA).Methods Immunohistochemistry was used to detect the PR-SET7 and PCNA expressions in esophageal cancer tissues and adjacent normal tissues of 32 cases between June 2010 and February 2011. The correlations between the expression of PR-SET7 and patients’ gender, age, degree of carcinoma tissue differentiation, TNM stages, lymph node metastasis and proliferation of tumor cells were analyzed.Results Immunohistochemistry Results showed that PR-SET7 and PCNA were mainly expressed in nuclear. The expression of PR-SET7 and PCNA in cancerous tissues was significantly stronger than in adjacent tissues. The high expression rate of PR-SET7 was 81.25%, but the expression was mostly low in adjacent tissues, where the high expression rate was 15.62%(P<0.01).PCNA index in cancer tissues was 68.12±16.03, normal tissues was 38.22±20.56,both comparative difference was statistically significint (P<0.05).PR-SET7 protein levels in patients with esophagus carcinoma were correlated with invasive depth and lymph node metastasis (P<0.05) rather than with age or gender (P>0.05).There was a significant correlation between the expression of PR-SET7 and PCNA index (rs=0.551,P=0.001).Conclusions There is an abnormal expression of PR-SET7 and PCNA during the development and progression of esophageal carcinoma. The expression level may be related to tumor progression, metastasis and prognosis. There is a significant correlation between PR-SET7 and PCNA overexpression in cancer tissues, which is of significance for exploration of the mechanism.
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Received: 10 October 2016
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[1] |
Xiao B, Jing C, Kelly G, et al. Specificity and mechanism of the histone methyltransferase Pr-Set7[J]. Genes Dev, 2005, 19(12): 1444-1454.
|
[2] |
Couture J F, Collazo E, Brunzelle J S, et al. Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase [J]. Genes Dev, 2005, 19(12): 1455-1465.
|
[3] |
王 静,徐金升. 赖氨酸甲基转移酶SET8结构和功能及其与肿瘤关系的研究进展[J]. 肿瘤防治研究, 2015, 42(4):403-406.
|
[4] |
Takawa M, Cho H S, Hayami S, et al. Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression [J]. Cancer Res, 2012, 72(13): 3217-3227.
|
[5] |
李俭杰, 邵 云,卫 星,等. P53和PCNA的表达与食管癌预后因素的临床观察[J].中国医刊, 2012, 47(5): 58-60.
|
[6] |
McCarty K S Jr, Miller L S, Cox E B, et al. Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies [J]. Arch Pathol Lab Med, 1985, 109(8): 716-721.
|
[7] |
Oda H, Hubner M R, Beck D B, et al. Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA-dependent degradation during DNA damage[J]. Mol Cell, 2010, 40(3): 364-376.
|
[8] |
Hsiao K Y,Mizzen C A. Histone H4 deacetylation facilitates 53BP1 DNA damage signaling and double-strand break repair [J]. J Mol Cell Biol, 2013, 5(3): 157-165.
|
[9] |
Oda H, Okamoto I, Murphy N, et al. Monomethylation of histone H4-lysine 20 is involved in chromosome structure and stability and is essential for mouse development [J]. Mol Cell Biol, 2009, 29(8): 2278-2295.
|
[10] |
Brustel J, Tardat M, Kirsh O, et al. Coupling mitosis to DNA replication : the emerging role of the histone H4-lysine 20 methyltransferase PR-Set7 [J]. Trends Cell Biol, 2011, 21(8): 452-460.
|
[11] |
Huen M S, Sy S M, Van Deursen J M, et al. Direct interaction between SET8 and proliferating cell nuclear antigen couples H4-K20 methylation with DNA replication [J]. J Biol Chem, 2008, 283(17):11073-11077.
|
[12] |
West L E, Roy S, Lachmi-Weiner K, et al. The MBT repeats of L3MBTL1 link SET8-mediated p53 methylation at lysine 382 to target gene repression [J]. J Biol Chem, 2010, 285(48): 37725-37732.
|
[13] |
Beck D B, Oda H, Shen S S, et al. PR-Set7 and H4K20me1:at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription[J]. Genes Dev, 2012, 26(4): 325-337.
|
[14] |
Kaniskan H U, Jin J. Chemical probes of histone lysine methyltransferases[J]. ACS Chem Biol, 2015, 10(1): 40-50.
|
[15] |
Copeland R A, Moyer M P, Richon V M, Targeting genetic alterations in protein methyltransferases for personalized cancer therapeutics [J]. Oncogene, 2013, 32(8): 939-946.
|
[16] |
Klose R J, Zhang Y. Regulation of histone methylation by demethylimination and demethy lation [J]. Nat Rev Mol Cell Biol, 2007, 8(4): 307-318.
|
[17] |
Okumura H, Uchikado Y, Setoyama T, et al. Biomarkers for predicting the response of esophageal squamous cell carcinoma to neoadjuvant chemoradiatgion therapy [J]. Surg Today, 2014, 44(3): 421-428.
|
|
|
|