Department of Radiation Oncology, Key Laboratory of Radiation Oncology of Shandong Province, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, People's Republic of China.
Med Oncol. 2012 Mar;29(1):113-8. doi: 10.1007/s12032-010-9768-9. Epub 2010 Dec 8.
A human oncoprotein-designed cancerous inhibitor of PP2A (CIP2A) has been recently identified, which can stabilize c-Myc protein by inhibiting its degradation mediated by protein phosphatase 2A (PP2A) in tumor cells and promote the proliferation of various cancer cells. Esophageal squamous cell carcinoma (ESCC) is a highly aggressive cancer with poor prognosis worldwide. However, the underlying molecular mechanism of the development of ESCC is still poorly understood. In the present study, the CIP2A expression between normal and malignant esophageal tissues was compared by immunohistochemical analysis; moreover, the mechanisms of CIP2A-mediated tumorigenesis were investigated by evaluating its role in cell proliferation, cell cycle, apoptosis and senescence. We found that the positive staining of CIP2A was found in 36 of 40 (90%) of cancer tissues, whereas only 8 of 40 (20%) normal esophageal mucosa exhibited positive CIP2A staining. The CIP2A is significantly overexpressed in human esophageal tumors when compared with normal tissues (χ(2) = 39.6, P < 0.01). On the other hand, the CIP2A expression was not associated with age, gender, tumor burden, or differentiation status. Depletion of CIP2A expression led to impaired clonogenicity and senescence, which is the primary mechanism of CIP2A in oncogenesis. Therefore, CIP2A may be a candidate in diagnosis and therapy of esophageal cancer.
一种人类致癌蛋白设计的 PP2A（CIP2A）抑制剂最近被发现，它可以通过抑制肿瘤细胞中蛋白磷酸酶 2A（PP2A）介导的 c-Myc 蛋白降解来稳定 c-Myc 蛋白，从而促进各种癌细胞的增殖。食管鳞状细胞癌（ESCC）是一种在全球范围内具有高度侵袭性和预后不良的癌症。然而，ESCC 发展的潜在分子机制仍知之甚少。在本研究中，通过免疫组织化学分析比较了正常和恶性食管组织中的 CIP2A 表达；此外，通过评估 CIP2A 在细胞增殖、细胞周期、细胞凋亡和衰老中的作用，研究了 CIP2A 介导的肿瘤发生机制。我们发现，在 40 例癌症组织中的 36 例（90%）中发现了 CIP2A 的阳性染色，而在 40 例正常食管黏膜中仅有 8 例（20%）显示出阳性 CIP2A 染色。与正常组织相比，CIP2A 在人类食管肿瘤中明显过表达（χ(2) = 39.6，P < 0.01）。另一方面，CIP2A 的表达与年龄、性别、肿瘤负荷或分化状态无关。CIP2A 表达的缺失导致克隆形成能力受损和衰老，这是 CIP2A 致癌的主要机制。因此，CIP2A 可能是诊断和治疗食管癌的候选物。
