Li W-H, Chang L, Xia Y-X, Wang L, Liu Y-Y, Wang Y-H, Jiang Z, Xiao J, Wang Z-R
Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu, PR China Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, PR China.
Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, PR China.
Int J Immunopathol Pharmacol. 2015 Mar;28(1):45-52. doi: 10.1177/0306419015572073.
Increased expression of pituitary tumor-transforming gene 1 (PTTG1) is expressed in many tumors and regulates tumor growth and progression. However, the precise function of PTTG1 in the tumorigenesis of lung adenocarcinoma (LAC) is not defined yet. Here, we examined the expression of PTTG1 in human LAC tissues by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was carried out to investigate the effects of lentiviral vector-mediated PTTG1 shRNA (shPTTG1) on cell growth and invasive potential in LAC cell lines (A549 and LETPα-2), assessed by MTT and Transwell assays. As a consequence, we found that the expression of PTTG1 protein was markedly upregulated in LAC tissues compared with the adjacent non-cancerous tissues (ANCT) (54.0% vs. 28.0%, P = 0.008), and was positively associated with the lymphatic invasion of the tumor (P = 0.01). Moreover, knockdown of PTTG1 expression inhibited tumor proliferation and invasion of LAC cells, companied by the decreased expression of CyclinD1 and MMP-2 and increased expression of p-TGFβ1 and p-SMAD3. Collectively, our findings indicate that high expression of PTTG1 is correlated with the tumor metastasis of LAC patients, and knockdown of PTTG1 suppresses the growth and invasion of LAC cells through upregulation of the TGFβ1/SMAD3 signaling, suggesting that PTTG1 may be a potential target for developing an effective immunotherapeutic strategy for LAC.
垂体肿瘤转化基因1（PTTG1）表达增加在许多肿瘤中都有体现，并调节肿瘤的生长和进展。然而，PTTG1在肺腺癌（LAC）发生中的精确功能尚未明确。在此，我们通过使用组织芯片技术的免疫组织化学分析检测了人LAC组织中PTTG1的表达。进行了功能丧失实验，以研究慢病毒载体介导的PTTG1短发夹RNA（shPTTG1）对LAC细胞系（A549和LETPα-2）中细胞生长和侵袭潜能的影响，通过MTT和Transwell实验进行评估。结果，我们发现与相邻非癌组织（ANCT）相比，LAC组织中PTTG1蛋白的表达明显上调（54.0%对28.0%，P = 0.008），并且与肿瘤的淋巴侵袭呈正相关（P = 0.01）。此外，PTTG1表达的敲低抑制了LAC细胞的肿瘤增殖和侵袭，同时伴随着细胞周期蛋白D1和基质金属蛋白酶-2表达的降低以及p-TGFβ1和p-SMAD3表达的增加。总体而言，我们的研究结果表明PTTG1的高表达与LAC患者的肿瘤转移相关，并且PTTG1的敲低通过上调TGFβ1/SMAD3信号通路抑制了LAC细胞的生长和侵袭，提示PTTG1可能是开发针对LAC的有效免疫治疗策略的潜在靶点。
