NGX6 gene inhibits cell proliferation and plays a negative role in EGFR pathway in nasopharyngeal carcinoma cells

作者:Wang, LL; Ma, J; Li, J; Li, XL; Zhang, QH; Peng, SP; Peng, C; Zhou, M; Xiong, W; Yang, JB; Zhou, J; Fan, SQ; Tan, C; Yan, Q; Shen, SR; Li, GY*
来源:Journal of Cellular Biochemistry, 2005, 95(1): 64-73.
DOI:10.1002/jcb.20393

摘要

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 GO-G, 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 GO-G, progression and thus inhibit cell proliferation by negatively regulating EGFR pathway in NPC cells and down-regulating the expression of cyclin D1 and E.