title: Reversed expression of GRIM-1 and GRP78 in human non-small cell lung cancer.
abstract: Gene associated with retinoid and interferon-induced mortality 1 (GRIM-1) acts as a tumor growth suppressor via apoptosis induction. However, GRIM-1 expression in human non-small cell lung cancer (NSCLC) and its potential interaction with another apoptosis-associated protein-glucose-regulated protein 78 (GRP78)-are as yet unknown. Using 40 surgical specimens, we showed significantly lower expression of GRIM-1 in NSCLC at both protein and messenger RNA (mRNA) levels compared with that in normal tissues (P < .01 and P < .001, respectively). Interestingly, these tumors tended to express higher basal amounts of GRP78 protein and mRNA (P < .05 and P < .001, respectively). Similarly, in the NSCLC tissues, weaker staining for GRIM-1 (main intensity + to ++) but stronger staining for GRP78 (main intensity +++ to ++++) was observed. Correlation analysis showed that protein and mRNA expression or the percentage of cells immunoreactive for GRIM-1 was negatively correlated with that of GRP78 (r = -0.279, r = -0.326, or r = -0.571, respectively). Coimmunoprecipitation and transient transfection revealed that GRIM-1 interacted with GRP78 and suppressed GRP78 protein expression. In addition, there was no correlation between GRIM-1 expression and clinical characteristics, whereas GRP78 expression was significantly correlated with tumor-nodes-metastasis (TNM) stage (stage 3 + 4 versus stage 1 + 2). In conclusion, the expression of GRIM-1 and GRP78 was negatively correlated in human NSCLC tissues, and the down-regulation of GRP78 by GRIM-1 provides a possible mechanism for their interaction. This study suggests a novel potential molecular pathway inactivated during the development of NSCLC.
authors: Department of Pulmonary Medicine, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China.
authors: Hui-Mei
authors: HM
authors: Wu
authors: Department of Pulmonary Medicine, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China.
authors: Zi-Feng
authors: ZF
authors: Jiang
authors: Department of Pulmonary Medicine, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China.
authors: Xiao-Yun
authors: XY
authors: Fan
authors: Department of Pulmonary Medicine, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China.
authors: Tong
authors: T
authors: Wang
authors: Department of Pulmonary Medicine, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China.
authors: Ke-Xu
authors: Department of Pulmonary Medicine, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China.
authors: Xue-Bo
authors: XB
authors: Yan
authors: School of Life Science, University of Science and Technology of China, Hefei 230027, Anhui, PR China.
authors: Yang
authors: Y
authors: Ma
authors: School of Life Science, University of Science and Technology of China, Hefei 230027, Anhui, PR China.
authors: Wei-Hua
authors: WH
authors: Xiao
authors: Department of Pulmonary Medicine, Anhui Geriatric Institute, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, PR China. Electronic address: rongyuliu@gmail.com.
authors: Rong-Yu
authors: RY
authors: Liu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C542388:SHQ1 protein, human; D025521:Tumor Suppressor Proteins
keywords: GRIM-1; GRP78; Interaction; Non–small cell lung cancer; Pathogenesis