title: Knockdown of PTTG1 inhibits the growth and invasion of lung adenocarcinoma cells through regulation of TGFB1/SMAD3 signaling.
abstract: 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.
authors: 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.
authors: W-H
authors: WH
authors: Li
authors: Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, PR China.
authors: L
authors: L
authors: Chang
authors: Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, PR China.
authors: Y-X
authors: YX
authors: Xia
authors: Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province, Kunming, PR China.
authors: L
authors: L
authors: Wang
authors: Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu, PR China.
authors: Y-Y
authors: YY
authors: Liu
authors: Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu, PR China.
authors: Y-H
authors: YH
authors: Wang
authors: Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu, PR China.
authors: Z
authors: Z
authors: Jiang
authors: Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu, PR China.
authors: J
authors: J
authors: Xiao
authors: Health Ministry Key Laboratory of Chronobiology, College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu, PR China wangzhengrong2014@163.com.
authors: Z-R
authors: ZR
authors: Wang
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D064249:Securin / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D051900:Smad3 Protein / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C497790:SMAD3 protein, human; D064249:Securin; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C578002:pituitary tumor-transforming protein 1, human; D019938:Cyclin D1; D020778:Matrix Metalloproteinase 2
keywords: growth; invasion; lung adenocarcinoma; pituitary tumor-transforming gene 1