细胞周期相关蛋白cyclin D1、p53和p21在食管鳞癌中的表达改变及其病理学意义

doi:10.3724/SP.J.1005.2010.00455

遗传 ›› 2010, Vol. 32 ›› Issue (5): 455-460.doi: 10.3724/SP.J.1005.2010.00455

细胞周期相关蛋白cyclin D1、p53和p21在食管鳞癌中的表达改变及其病理学意义

林德晨¹, 史志周¹, 薛丽燕², 陈微¹, 徐昕¹, 韩亚玲¹, 吕宁², 王明荣¹

1. 中国医学科学院北京协和医学院肿瘤医院肿瘤研究所分子肿瘤学国家重点实验室, 北京 100021;
2. 中国医学科学院北京协和医学院肿瘤医院病理科, 北京 100021

收稿日期:2010-01-15 修回日期:2010-03-14 出版日期:2010-05-20 发布日期:2010-05-15
通讯作者: 王明荣 E-mail:wangmr04@126.com
基金资助:
国家科技支撑计划(编号：2006BAI02A14)和863计划重大专项(编号：2006AA02A403)资助

Expression of cell cycle related proteins cyclin D1, p53 and p21 in esophageal squamous cell carcinoma

LIN De-Chen¹, SHI Zhi-Zhou¹, XUE Li-Yan², CHEN Wei¹, XU Xin¹, HAN Ya-Ling¹, LV Ning², WANG Ming-Rong¹

1. State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China;
2. Department of Pathology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China

Received:2010-01-15 Revised:2010-03-14 Online:2010-05-20 Published:2010-05-15
Contact: Mingrong Wang E-mail:wangmr04@126.com

摘要/Abstract

摘要：

食管鳞状细胞癌(Esophageal squamous cell carcinoma, ESCC)是我国常见的恶性肿瘤之一, 虽然临床诊治手段正逐步改进, 但中晚期患者5年生存率仍然很低。目前认为细胞周期调控异常与肿瘤发生发展关系密切, 然而相关周期调节蛋白在食管癌患者中的表达改变、临床意义及其应用价值还没有明确结论。文章应用组织微阵列联合免疫组织化学技术(TMA-IHC), 对148例食管鳞癌组织标本中细胞G₁/S期调控蛋白cyclin D1、p53和p21^WAF1/Cip1的表达进行检测, 分析其与临床病理参数之间的相关性。结果显示, cyclin D1与p53蛋白在食管癌细胞中表达升高, p53表达阳性率与区域淋巴结转移显著相关(P = 0.001)。p21^WAF1/Cip1蛋白在肿瘤组织中表达降低, 且p21WAF1/Cip1表达阴性患者的术后生存时间显著短于表达阳性的患者(P = 0.001)。多因素生存分析显示p21WAF1/Cip1是一个独立的预后因素(相对危险度为0.418, P<0.001)。微阵列比较基因组杂交(array-CGH)检测进一步表明45.4%的食管癌患者存在cyclin D1基因扩增。以上结果提示食管鳞癌中存在细胞周期G1/S期调控异常, p21^WAF1/Cip1蛋白可能是一个有应用价值的预后因子。

关键词: 食管鳞状细胞癌, 细胞周期, 免疫组化, 组织微阵列, 预后判断

Abstract:

Dysregulation of cell cycle control, especially G₁/S phase transition, is implicated in the pathogenesis of most human cancers, including esophageal squamous cell carcinoma (ESCC). However, the clinicopathological significance of aberrant expression of G₁/S phase-related proteins in ESCC remains unclear. In the present study, cyclin D1, p21^WAF1/Cip1and p53 protein expression were examined in 148 ESCC cases using immunohistochemistry combined with tissue microarray. We then analyzed the correlations between their expression and clinicopathological parameters and found that overexpression of p53 was associated with lymph node metastasis (P = 0.001). p21^WAF1/Cip1down-regulation was an independent prognostic factor by multivariate analysis (RR = 0.418, P <0 .001). Further more, array-CGH results revealed that cyclin D1 gene was amplified in 45.4% of ESCC patients. This study confirms that dysregulation of G1/S related genes is common in ESCC and reduced expression of p21^WAF1/Cip1 protein can predict shorter overall survival time of patients with ESCC.

Key words: esophageal squamous cell carcinoma, cell cycle regulation, immunohistochemistry, tissue microarray, prognosis

林德晨，史志周，薛丽燕，陈微，徐昕，韩亚玲，吕宁，王明荣. 细胞周期相关蛋白cyclin D1、p53和p21在食管鳞癌中的表达改变及其病理学意义[J]. 遗传, 2010, 32(5): 455-460.

LIN De-Chen, SHI Zhi-Zhou, XUE Li-Yan, CHEN Wei, XU Cuan, HAN E-Ling, LV Ning, WANG Meng-Rong. Expression of cell cycle related proteins cyclin D1, p53 and p21 in esophageal squamous cell carcinoma[J]. HEREDITAS, 2010, 32(5): 455-460.

参考文献

[1] Roncalli M, Bosari S, Marchetti A, Buttitta F, Bossi P, Graziani D, Peracchia A, Bonavina L, Viale G, Coggi G. Cell cycle-related gene abnormalities and product expression in esophageal carcinoma. Lab Invest, 1998, 78(9): 1049–1057.

[2] Shao L, Hittelman WN, Lin J, Yang H, Ajani JA, Wu X. Deficiency of cell cycle checkpoints and DNA repair sys-tem predispose individuals to esophageal cancer. Mutat Res, 2006, 602(1–2): 143–150.

[3] Shinohara M, Aoki T, Sato S, Takagi Y, Osaka Y, Koyanagi Y, Hatooka S, Shinoda M. Cell cycle-regulated factors in eso-phageal cancer. Dis Esophagus, 2002, 15(2): 149–154.

[4] Paulson TG, Galipeau PC, Xu L, Kissel HD, Li X, Blount PL, Sanchez CA, Odze RD, Reid BJ. p16 mutation spec-trum in the premalignant condition Barrett's esophagus. PloS One, 2008, 3(11): e3809.

[5] Fang JY, Lu YY. Effects of histone acetylation and DNA methylation on p21( WAF1) regulation. World J Gastro-enterol, 2002, 8(3): 400–405.

[6] Amanullah A, Hoffman B, Liebermann DA. Deregulated E2F-1 blocks terminal differentiation and loss of leuke-mogenicity of M1 myeloblastic leukemia cells without abrogating induction of p15(INK4B) and p16(INK4A). Blood, 2000, 96(2): 475–482.

[7] Zhang G, Zhou X, Xue L, Quan L, Wang Y, Zhou C, Lu N, Wang Q, Zhu H, Xu N. Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int, 2005, 55(6): 310–317.

[8] Natsugoe S, Nakashima S, Matsumoto M, Xiangming C, Okumura H, Kijima F, Ishigami S, Takebayashi Y, Baba M, Takao S, Aikou T. Expression of p21^WAF1/Cip1in the p53-dependent pathway is related to prognosis in patients with advanced esophageal carcinoma. Clin Cancer Res, 1999, 5(9): 2445–2449.

[9] Mega S, Miyamoto M, Ebihara Y, Takahashi R, Hase R, Li L, Shichinohe T, Kawarada Y, Uehara H, Kaneko H, Hashimoto H, Murakami Y, Itoh T, Morikawa T, Kondo S. Cyclin D1, E2F1 expression levels are associated with characteristics and prognosis of esophageal squamous cell carcinoma. Dis Esophagus, 2005, 18(2): 109–113.

[10] Wei F, Ni J, Wu SS, Liu H, Xu X, Han YL, Cai Y, Zhang JW, Chen XJ, Pang H, Lu N, Ji L, Wu M, Wang MR. Cytogenetic studies of esophageal squamous cell carcinomas in the north-ern Chinese population by comparative genomic hybridiza-tion. Cancer Genet Cytogenet, 2002, 138(1): 38–43.

[11] He YT, Hou J, Qiao CY, Chen ZF, Song GH, Li SS, Meng FS, Jin HX, Chen C. An analysis of esophageal cancer in-cidence in Cixian county from 1974 to 1996. World J Gastroenterol, 2003, 9(2): 209–213.

[12] Pesutic-Pisac V, Punda A, Gluncic I, Bedekovic V, Pranic-Kragic A, Kunac N. Cyclin D1 and p27 expression as prognostic factor in papillary carcinoma of thyroid: as-sociation with clinicopathological parameters. Croat Med J, 2008, 49(5): 643–649.

[13] Aaltonen K, Amini RM, Landberg G, Eerola H, Aittomaki K, Heikkila P, Nevanlinna H, Blomqvist C. Cyclin D1 ex-pression is associated with poor prognostic features in es-trogen receptor positive breast cancer. Breast Cancer Res Treat, 2009, 113(1): 75–82.

[14] Ikeguchi M, Sakatani T, Ueta T, Kaibara N. Cyclin D1 expression and retinoblastoma gene protein (pRB) expres-sion in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol, 2001, 127(9): 531–536.

[15] Nakamura T, Ide H, Eguchi R, Hayashi K, Takasaki K. Concomitant analysis of p16/INK4, cyclin D1, and retino-blastoma protein expression in esophageal squamous cell car-cinoma. Hepatogastroenterology, 2003, 50(53): 1321–1326.

[16] Jang KT, Chae SW, Sohn JH, Park HR, Shin HS. Coex-pression of MUC1 with p53 or MUC2 corr

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

细胞周期相关蛋白cyclin D1、p53和p21在食管鳞癌中的表达改变及其病理学意义

Expression of cell cycle related proteins cyclin D1, p53 and p21 in esophageal squamous cell carcinoma

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	王翠玲, 刘信燚, 王亚会, 张争, 王治东, 周钢桥. MCM2通过抑制p53信号通路促进胆管癌细胞的增殖、迁移和侵袭[J]. 遗传, 2022, 44(3): 230-244.
[2]	张雨, 方玉达. Cohesin结构及功能研究进展[J]. 遗传, 2020, 42(1): 57-72.
[3]	陈家辉, 任学义, 李丽敏, 卢诗意, 程湉, 谭量天, 梁少东, 何丹林, 罗庆斌, 聂庆华, 张细权, 罗文. 转录组测序揭示细胞周期通路参与鸡腹脂沉积[J]. 遗传, 2019, 41(10): 962-973.
[4]	梁新全，杜贻鹏，王东来，杨洋. 赖氨酸甲基转移酶PR-SET7及其生物学功能[J]. 遗传, 2013, 35(3): 241-254.
[5]	韩秋悦，范彦会，王雅丽，张少丹，韩春雨. BEX2与INI1/hSNF5蛋白的相互作用及其在细胞周期中的功能鉴定[J]. 遗传, 2012, 34(6): 711-718.
[6]	刘军，周常文，韦秋兰，庄建龙，林炤华，郑杰辉. 成年大脑神经细胞特异性ADAM10基因敲除小鼠模型的建立与鉴定[J]. 遗传, 2012, 34(12): 1570-1576.
[7]	顾娟，陈晓萍. 神经发育中的细胞周期时程[J]. 遗传, 2011, 33(11): 1185-1190.
[8]	刘双虎，王守志，张慧，李辉. 视网膜母细胞瘤基因1(RB1)研究进展[J]. 遗传, 2010, 32(11): 1097-1104.
[9]	康维，姚汉清，房丽丽，蔡岩，韩亚铃，徐昕，张钰，贾雪梅，王明荣 . 食管鳞癌3、8、10、20和Y染色体的非整倍性分析[J]. 遗传, 2009, 31(3): 255-260.
[10]	黄剑，沈海龙，刘长莉，李玉花. 植物不定芽离体再生分子调控的评述[J]. 遗传, 2007, 29(5): 528-528―536.
[11]	张德福，刘东，汤琳琳，王英，陈茵，王凯，王根林，KARL Schellander5，LIN Cailu5. 不同供体细胞及其处理对猪核移植重构胚体外发育的影响[J]. 遗传, 2007, 29(2): 211-211―217.
[12]	张晓娟，郭炜，王娜，周荣秒，董秀娟，李琰. MMP-13基因多态性与食管癌、贲门癌遗传易感性的关联研究[J]. 遗传, 2006, 28(12): 1500-1500~1504.
[13]	李艳凤，张强，朱大海. 泛素介导的蛋白质降解与肿瘤发生[J]. 遗传, 2006, 28(12): 1591-1591~1596.
[14]	朱益民，林洁，陈俭，黄琼，邵丽娜，来茂德. Staufen基因在结直肠癌组织中的表达[J]. 遗传, 2005, 27(5): 705-709.
[15]	刘丽英，金春莲，林长坤，武盈玉，孙开来. 应用胎儿特异性抗体HbF（γ链）标记法无创性产前基因诊断DMD[J]. 遗传, 2005, 27(1): 49-52.