NGX6 gene inhibits cell proliferation and plays a negative role in EGFR pathway in nasopharyngeal carcinoma cells.
Nasopharyngeal carcinoma (NPC) is a common cancer in South China but is rare in other parts of the world. A novel NPC-related gene was isolated by location candidate cloning strategy, whose expression was down-regulated in NPC. This gene was designated human NGX6 (Genbank accession AF188239) and encoded a predicted protein of 338 amino acids that harbors an EGF-like domain. The effects of NGX6 on cells from human NPC cell line HNE1 were investigated. The cells transfected with NGX6 had a markedly high expression of NGX6, leading to significant decrease in cell proliferation and the capability to form colonies in soft agar, delaying the G0-G1 cell cycle progression. Flow cytometry assay indicated that the expression of cyclin D1 significantly decreased in NGX6-transfected HNE1 cells as well as cyclin A and E. There was a delay in tumor formation and a dramatic reduction in tumor size when cells transfected with NGX6 were injected into nude mice. In another way, we found NGX6 played a negative role in EGFR Ras/Mek/MAPK pathway. We propose that NGX6, as an EGF-like domain gene, could delay cell cycle G0-G1 progression and thus inhibit cell proliferation by negatively regulating EGFR pathway in NPC cells and down-regulating the expression of cyclin D1 and E.
Wang
Lili
L
Cancer Research Institute, Xiang-Ya School of Medicine, Central South University, Changsha, Hunan, 410078, China.
Ma
Jian
J
Li
Jiang
J
Li
Xiaoling
X
Zhang
Qiuhong
Q
Peng
Shuping
S
Peng
Cong
C
Zhou
Ming
M
Xiong
Wei
W
Yang
Jianbo
J
Zhou
Jie
J
Fan
Songqing
S
Tan
Chen
C
Yan
Qun
Q
Shen
Shourong
S
Li
Guiyuan
G
D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056741:Cyclin D; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D056741:Cyclin D; D016213:Cyclins; D008565:Membrane Proteins; C477325:TMEM8B protein, human; D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors