Evidence of increased Id-1 expression and its role in cell proliferation in nasopharyngeal carcinoma cells.
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.
Wang
Xianghong
X
Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong, SAR, China.
Xu
Kexin
K
Ling
Ming Tat
MT
Wong
Y C
YC
Feng
Hui Chen
HC
Nicholls
John
J
Tsao
S W
SW
D042846:CDC2-CDC28 Kinases; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D016895:Culture Media, Serum-Free; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012016:Reference Values; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
C436291:CDKN1B protein, human; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases