title: RASSF4 is downregulated in nonsmall cell lung cancer and inhibits cancer cell proliferation and invasion.
abstract: RASSF4 has been implicated as a tumor suppressor in several human cancers. Its clinical significance and biological characteristics in human nonsmall cell lung cancer (NSCLC) have not been explored yet. In this study, we explored expression pattern of RASSF4 in 89 NSCLC specimens. The results showed that RASSF4 was downregulated in 36/89 NSCLC tissues compared with normal tissue. RASSF4 downregulation significantly associated with advanced TNM stage, positive nodal status, and poor prognosis. We examined RASSF4 protein expression in normal lung epithelial cell line and lung cancer lines. We found that RASSF4 expression was downregulated in four of seven lung cancer cell lines compared with normal bronchial epithelial cells. RASSF4 plasmid transfection was performed in H460 and A549 cell lines. RASSF4 overexpression inhibited proliferation, colony formation, and invading ability. In addition, we identified that RASSF4 could inhibit cell cycle progression with downregulation of cyclin D1. Expression of invasion-related protein MMP2, MMP9 was also decreased. In conclusion, the present study suggested that RASSF4 serves as an important tumor suppressor in NSCLC.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, 110001, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, 110001, China.
authors.forename: Qianze
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, 110001, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, 110001, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, 110001, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, 110001, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, 110001, China. wangenhuacmu@hotmail.com.
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C495500:RASSF4 protein, human; D025521:Tumor Suppressor Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Invasion; Nonsmall cell lung cancer; Proliferation; RASSF4