Du Guang-Sheng, Wang Jian-Ming, Lu Jin-Xi, Li Qiang, Ma Chao-Qun, Du Ji-Tao, Zou Sheng-Quan
Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ann Surg Oncol. 2009 Jun;16(6):1578-86. doi: 10.1245/s10434-009-0423-7. Epub 2009 Mar 17.
Atypical protein kinase C iota (aPKC-iota) and its associated intracellular molecules, E-cadherin and beta-catenin, are important for cell polarization in tumorigenesis and progression. Expression of aPKC-iota, P-aPKC-iota (activated aPKC-iota), E-cadherin, and beta-catenin in hepatocellular carcinoma (HCC) was measured, and correlation with clinicopathological characteristics of HCC was analyzed.
Paraffin-embedded tumor tissue was obtained from patients with HCC after resection without preoperative radiotherapy or chemotherapy. Gene expression was detected by polymerase chain reaction (PCR), and protein expression was detected by immunohistochemistry and Western blot analysis. Expressions of aPKC-iota, P-aPKC-iota, E-cadherin, and beta-catenin were analyzed with relation to the clinicopathological data.
The gene and protein expression of aPKC-iota are obviously higher in HCC tissues than that in peritumoral tissues and normal tissues by semiquantitative PCR and immunohistochemistry methods. Accumulation of aPKC-iota in HCC cytoplasm and nucleolus inhibited the later formation of belt-like adherens junctions (AJs) and/or tight junctions (TJs) in cell-cell contact. E-cadherin was reduced and accumulation of cytoplasm beta-catenin was increased in HCC. The expression of aPKC-iota was closely related to pathological differentiation, tumor size, invasion, and metastasis of HCC.
Accumulation of cytoplasm aPKC-iota may reflect pathological differentiation, invasion, and metastasis potential of HCC. In this regard, our study on HCC revealed the potential usefulness of aPKC-iota, E-cadherin, and beta-catenin as a prognostic marker, closely related to pathological differentiation, invasion, metastasis, and prognosis of HCC.
非典型蛋白激酶Cι（aPKC-ι）及其相关的细胞内分子E-钙黏蛋白和β-连环蛋白在肿瘤发生和进展过程中的细胞极化中起重要作用。检测肝细胞癌（HCC）中aPKC-ι、磷酸化aPKC-ι（活化的aPKC-ι）、E-钙黏蛋白和β-连环蛋白的表达，并分析其与HCC临床病理特征的相关性。
收集未经术前放疗或化疗的HCC患者术后切除的石蜡包埋肿瘤组织。采用聚合酶链反应（PCR）检测基因表达，免疫组织化学和蛋白质印迹分析检测蛋白质表达。分析aPKC-ι、磷酸化aPKC-ι、E-钙黏蛋白和β-连环蛋白的表达与临床病理数据的关系。
通过半定量PCR和免疫组织化学方法检测发现，HCC组织中aPKC-ι的基因和蛋白表达明显高于瘤旁组织和正常组织。HCC细胞质和核仁中aPKC-ι的积累抑制了细胞间接触中带状黏附连接（AJs）和/或紧密连接（TJs）的后期形成。HCC中E-钙黏蛋白减少，细胞质β-连环蛋白积累增加。aPKC-ι的表达与HCC的病理分化、肿瘤大小、侵袭和转移密切相关。
细胞质中aPKC-ι的积累可能反映HCC的病理分化、侵袭和转移潜能。在这方面，我们对HCC的研究揭示了aPKC-ι、E-钙黏蛋白和β-连环蛋白作为预后标志物的潜在用途，它们与HCC的病理分化、侵袭、转移和预后密切相关。
