Cancerous inhibitor of protein phosphatase 2A is overexpressed in cervical cancer and upregulated by human papillomavirus 16 E7 oncoprotein
Cancerous inhibitor of protein phosphatase 2A is overexpressed in cervical cancer and upregulated by human papillomavirus 16 E7 oncoprotein
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蛋白磷酸酶 2A 的癌性抑制剂在宫颈癌中过度表达，并被人乳头瘤病毒 16 E7 癌蛋白上调
DOI：
10.1016/j.ygyno.2011.04.031
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发表时间：
2011-08-01
影响因子：
4.7
通讯作者：
Zhao, Weiming
中科院分区：
文献类型：
--
作者：
Liu, Juan;Wang, Xiao;Zhao, Weiming
目标.蛋白磷酸酶2A（CIP 2A）是近年来发现的一种稳定c-Myc并促进细胞增殖和转化的癌蛋白。在这里，我们研究了CIP 2A在体内和体外宫颈癌中的作用。通过免疫组织化学和RT-PCR评估正常宫颈、宫颈上皮内瘤变（CIN）I至III和宫颈癌组织中的CIP 2A表达。通过HeLa中的siRNA抑制CIP 2A后，通过细胞增殖测定、集落形成测定和软琼脂中的锚定非依赖性生长来探索细胞生长。SiHa和Caski细胞。采用免疫组化方法检测宫颈癌组织中CIP 2A与HPV 16 E7的相互作用，并在SiHa细胞中应用siRNA抑制HPV 16 E7后，通过实时荧光定量PCR和Western blot检测CIP 2A与HPV 16 E7的相互作用。CIP 2A在73.3%的宫颈癌组织（n = 15）中有转录，而在正常宫颈组织（n = 8）中无转录。CIP 2A蛋白在52.8%的宫颈癌（n = 72）和12.5%的CIN III组织（n = 24）中被检测到，但在正常（n = 15）、CIN I（n = 21）或CIN II（n = 25）样品中未被检测到。宫颈癌组织中CIP 2A蛋白水平与HPV 16 E7水平呈正相关。CIP 2A表达在E7耗尽后显著降低。此外，CIP 2A缺失降低了c-Myc蛋白水平，并损害了宫颈癌细胞的增殖和生长。CIP 2A在宫颈癌中过表达，并促进宫颈癌细胞的恶性生长。其表达被HPV 16 E7上调。因此，CIP 2A在宫颈癌的发生发展中起着重要作用，在宫颈癌的诊断和治疗中具有重要的应用前景。(C)2011 Elsevier Inc. All rights reserved.
Objectives. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein stabilizing c-Myc and promoting cell proliferation and transformation. Here we investigated the role of CIP2A in cervical cancer in vivo and in vitro.Methods. CIP2A expression was assessed in normal cervical, cervical intraepithelial neoplasia (CIN) I to III and cervical cancer tissues by immunohistochemistry and RT-PCR Cell growth was explored by cell proliferation assay, colony formation assay and anchorage-independent growth in soft agar after inhibition of CIP2A by siRNA in HeLa. SiHa and Caski cells. Crosstalk of CIP2A and HPV16 E7 was investigated by immunohistochemistry in cervical cancer tissues and by real-time PCR and western blot analysis after HPV16 E7 inhibition by siRNA in SiHa cells.Results. CIP2A was transcribed in 73.3% of cervical cancer tissues (n = 15) but not in normal cervical tissues (n = 8). CIP2A protein was detected in 52.8% of cervical cancer (n = 72) and 12.5% of CIN III tissues (n = 24) but not in normal (n = 15), CIN I (n = 21) or CIN II samples (n = 25). CIP2A protein level was positively associated with HPV16 E7 level in cervical cancer tissues. CIP2A expression was markedly reduced after E7 depletion. Moreover, CIP2A depletion reduced c-Myc protein level and impaired proliferation and growth of cervical cancer cells.Conclusions. CIP2A is overexpressed in cervical cancer and promotes the malignant growth of cervical cancer cells. Its expression is upregulated by HPV16 E7. Therefore, CIP2A plays an important role in carcinogenisis of cervical cancer and shows promise for the diagnosis and treatment of cervical cancer. (C) 2011 Elsevier Inc. All rights reserved.