Evidence of increased Id-1 expression and its role in cell proliferation in nasopharyngeal carcinoma cells.

Abstract

Inhibitor of differentiation or DNA binding (Id-1), a helix-loop-helix transcription factor, has recently been shown to inactivate the retinoblastoma (RB)/p16(INK4a) pathway through down-regulation of p16(INK4a) and increasing phosphorylation of RB in certain cell types. Nasopharyngeal carcinoma (NPC) is a common cancer in Hong Kong, and inactivation of the tumor suppressor RB at transcription level is a rare event in NPC. The objective of this study was to investigate the role of Id-1 in NPC cell proliferation and its expression in NPC samples. An NPC cell line, CNE1, was transfected with a retroviral vector containing a full-length Id-1 cDNA, and six stable transfectant clones were isolated with differential Id-1 expression levels. The effect of ectopic Id-1 expression on serum-independent cell growth, cell-cycle distribution, and expression of proteins associated with RB pathway was studied. The Id-1 expression in five NPC samples was also investigated using immunohistochemistry. Ectopic Id-1 expression in CNE1 cells resulted in an increase in serum-independent cell growth, percentage of cells in S phase, and phosphorylation of RB and cyclin-dependent kinase 2 proteins. In addition, immunohistochemical studies on NPC samples showed that expression of Id-1 was present in NPC cells but absent in normal tissues. This study demonstrates that Id-1 plays an important role in cell proliferation in NPC cells, and our results provide evidence for the first time of the significance of Id-1 expression in NPC cells and suggest a possible role of Id-1 expression in the inactivation of RB and development of NPC.