Kuramochi Junichi, Arai Takehiro, Ikeda Satoshi, Kumagai Jiro, Uetake Hiroyuki, Sugihara Kenichi
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
J Surg Oncol. 2006 Aug 1;94(2):155-60. doi: 10.1002/jso.20510.
Peptidyl prolyl cis-trans isomerase (Pin1) isomerizes only phosphorylated serine or threonine residues preceding proline in certain proteins and affects the protein function. Pin1 interacts with many signaling pathways, including Wnt signaling pathway that is crucial for colorectal tumorigenesis. Pin1 promotes cyclin D1 over-expression directly or through the stabilization of beta-catenin. Pin1 is over-expressed in some cancers such as prostate and breast cancers. This study aimed to determine whether Pin1 plays a role in colorectal tumorigenesis through the upregulation of beta-catenin and cyclin D1.
Immunohistochemical analyses were performed on 105 colorectal cancer tissue samples using anti-Pin1, anti-beta-catenin, and anti-cyclin D1 antibodies. We examined the relationships between Pin1 expression and clinicopathological factors, prognosis, and beta-catenin/cyclin D1 expression.
High Pin1 expression was observed in 40 cases (38%) and positively correlated with histological type (P=0.0240), depth of invasion (P=0.0051), and staging (P=0.0027) of colorectal tumors. High Pin1 expression was also correlated with the over-expressions of both beta-catenin (P=0.0225) and cyclin D1 (P=0.0137).
These results suggest that Pin1 plays an important role in colorectal tumorigenesis, presumably by increasing beta-catenin and cyclin D1 expressions.
肽基脯氨酰顺反异构酶(Pin1)仅使某些蛋白质中脯氨酸之前的磷酸化丝氨酸或苏氨酸残基发生异构化,从而影响蛋白质功能。Pin1与多种信号通路相互作用,包括对结直肠癌发生至关重要的Wnt信号通路。Pin1直接或通过稳定β-连环蛋白促进细胞周期蛋白D1的过度表达。Pin1在一些癌症如前列腺癌和乳腺癌中过度表达。本研究旨在确定Pin1是否通过上调β-连环蛋白和细胞周期蛋白D1在结直肠癌发生中发挥作用。
使用抗Pin1、抗β-连环蛋白和抗细胞周期蛋白D1抗体对105例结直肠癌组织样本进行免疫组织化学分析。我们研究了Pin1表达与临床病理因素、预后以及β-连环蛋白/细胞周期蛋白D1表达之间的关系。
40例(38%)观察到高Pin1表达,其与结直肠癌的组织学类型(P = 0.0240)、浸润深度(P = 0.0051)和分期(P = 0.0027)呈正相关。高Pin1表达也与β-连环蛋白(P = 0.0225)和细胞周期蛋白D1(P = 0.0137)的过度表达相关。
这些结果表明Pin1在结直肠癌发生中起重要作用,可能是通过增加β-连环蛋白和细胞周期蛋白D1的表达来实现的。