Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff, U.K.
Cancer Genomics Proteomics. 2012 Sep-Oct;9(5):321-7.
Signal-induced proliferation-associated gene 1 (SIPA1) codes for a GTPase-activating protein, known to be a negative regulator of Ras-related Protein (RAP) which belongs to the Ras superfamily. It has been implicated in certain malignancies, including leukemia, cervical cancer and breast cancer. However the role of this molecule in colorectal cancer remains unknown. The current study aimed to investigate the expression of SIPA1 in colorectal tumour tissues and its impact on the function of colorectal cancer cells.
A total of 94 colorectal cancer tissues together with 80 normal background tissues were used to examine the expression of SIPA1 transcript and protein using real-time quantitative Polymerase Chain Reaction (PCR) and immunohistochemical methods, respectively. Any association with clinical and histopathological characteristics was then identified. Ribozyme transgenes targeting SIPA1 were prepared to knockdown the expression of SIPA1 in colorectal cancer cells. The impact on their functions was subsequently determined, using respective in vitro function assays.
An increased expression of SIPA1 was evident in colorectal cancer tissues compared with its expression in normal background tissues (p<0.001). In colorectal tumours, its expression appeared to be lower in poorly-differentiated samples and in patients who had lymphatic metastasis. Knockdown of SIPA1 in colorectal cancer cells resulted in reduced cell growth in vitro. The knockdown exhibited a contrasting effect on invasion and migration, both of which were increased in SIPA1-knockdown cells compared with the controls.
SIPA1 is up-regulated in colorectal cancer. This suggests that SIPA1 plays diverse roles during disease progression as has contrasting effects on growth and motility of colorectal cancer cells.
信号诱导增殖相关基因 1（SIPA1）编码一种 GTP 酶激活蛋白，已知其为 Ras 相关蛋白（RAP）的负调节剂，RAP 属于 Ras 超家族。它已被牵涉到某些恶性肿瘤中，包括白血病、宫颈癌和乳腺癌。然而，这种分子在结直肠癌中的作用尚不清楚。本研究旨在研究 SIPA1 在结直肠肿瘤组织中的表达及其对结直肠癌细胞功能的影响。
使用实时定量聚合酶链反应（PCR）和免疫组织化学方法，分别检查了 94 例结直肠癌组织和 80 例正常背景组织中 SIPA1 转录本和蛋白质的表达。然后确定与临床和组织病理学特征的任何关联。制备了针对 SIPA1 的核酶转基因以敲低结直肠癌细胞中 SIPA1 的表达。随后使用各自的体外功能测定来确定对其功能的影响。
与正常背景组织相比，结直肠癌组织中 SIPA1 的表达明显增加（p<0.001）。在结直肠肿瘤中，其表达似乎在低分化样本和有淋巴转移的患者中较低。结直肠癌细胞中 SIPA1 的敲低导致体外细胞生长减少。敲低对侵袭和迁移表现出相反的影响，与对照组相比，SIPA1 敲低细胞中的侵袭和迁移均增加。
SIPA1 在结直肠癌中上调。这表明 SIPA1 在疾病进展过程中发挥多种作用，对结直肠癌细胞的生长和运动具有相反的影响。
