The transcription factor DEC1 (BHLHE40/STRA13/SHARP-2) is negatively associated with TNM stage in non-small-cell lung ca
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RESEARCH ARTICLE
The transcription factor DEC1 (BHLHE40/STRA13/ SHARP-2) is negatively associated with TNM stage in non-small-cell lung cancer and inhibits the proliferation through cyclin D1 in A549 and BE1 cells Yang Liu & Liang Wang & Xu-Yong Lin & Jian Wang & Juan-Han Yu & Yuan Miao & En-Hua Wang
Received: 23 November 2012 / Accepted: 4 February 2013 / Published online: 20 February 2013 # International Society of Oncology and BioMarkers (ISOBM) 2013
Abstract The objective of the current study was to investigate the expression pattern and clinicopathological significance of differentiated embryo–chondrocyte-expressed gene 1 (DEC1) in patients with non-small-cell lung cancer (NSCLC). In 118 archived NSCLC tissues, the positive rate of DEC1 was reduced in human lung cancer samples (36/118, 30.5 %) compared with adjacent normal lung tissues (106/118, 89.8 %), as measured by immunohistochemical staining. Loss of DEC1 was correlated with poor differentiation (p = 0.005) and high p-TNM stage (p = 0.002). Consistently, downregulation of DEC1 by siRNA knockdown promoted the growth and colony formation in the A549 lung cancer cell line, and overexpression of DEC1 inhibited the growth and colony formation in the BE1 lung cancer cell line. In addition, a significant negative correlation was found between DEC1 and cyclin D1 (p= 0.014) in 118 cases of NSCLC. Knockdown of DEC1 resulted in the upregulation of cyclin D1, and overexpression of DEC1 led to the downregulation of cyclin D1. Together with the observation that DEC1 bound directly to the promoter region of cyclin D1 in A549 cells, these results indicate that loss of DEC1 may promote tumor progression in NSCLC through upregulation of cyclin D1, and DEC1 might serve as a novel therapeutic target of NSCLC. Y. Liu : L. Wang : X.-Y. Lin : J. Wang : J.-H. Yu : Y. Miao : E.-H. Wang (*) Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang 110001, China e-mail: [email protected] Y. Liu : L. Wang : X.-Y. Lin : J. Wang : J.-H. Yu : Y. Miao : E.-H. Wang Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, China
Keywords Differentiated embryo-chondrocyte expressed gene 1 . Cyclin D1 . Non-small-cell lung cancer . Immunohistochemistry . Proliferation
Introduction Lung cancer is the leading cause of death among the malignant tumors worldwide, and the incidence of lung cancer is increasing [1]. Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small cell lung cancer (SCLC). Compared with SCLC, NSCLCs have better prognosis but are relatively insensitive to chemotherapy. When possible, NSCLC are primarily treated by surgical resection with curative intent. Large cell neuroendocrine cancer (LCNEC) is an unusual NSCLC subtype which displays morphologic and immunohistochemical characteristics similar to large-cell carcinomas and neuroendocrine tumors, respectively. However, the prognosis of LCNEC is generally worse than other NSCLCs. Although
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