Abstract
Nasopharyngeal carcinoma (NPC) is one of the most commons cancers in Southeast Asia and Southern China. Several NPC-associated genes have been so far described and here we describe the identification and the characterization of a novel nasopharyngeal carcinoma-associated peptide: NAP-1. NAP-1 was identified with the human genome draft searching method combined with nested PCR mapping of the chromosome 4q13 region. NAP-1 encodes an 85 amino acid alkaline peptide with a calculated isoelectric point of 9.3, three phosphorilation sites and a proline-rich region. Northern blot analysis revealed that NAP-1 is expressed as a 0.6 kb transcript in normal lymph nodes and trachea. In addition, reverse transcription (RT)-PCR showed that NAP-1 is expressed not only in NPC but in normal nasopharynx (NP) and various other tumors and tissues of the head and neck including: tonsils, lymph nodes, carcinoma of the tonsil, T cell lymphomas, squamous cell carcinoma of the hard palate, papilloma of the nasopharynx, nasopharyngitis, lymphoma of the tongue root and follicular dendritic cells (FDC). In addition, NAP-1 is not expressed in normal tissues or tumors from other anatomical regions and was not expressed by NPC cell lines. Surprisingly, differential RT-PCR demonstrated decreased expression of NAP-1 in NPC compared with paired NP biopsies in 42.5 % of cases (17 out of 40). In addition, in situ hybridization and immunohistochemistry demonstrated that NAP-1 is expressed by S100+ CD35+ FDCs of the germinal center and not in other normal immune cells infiltrating NP or NPC. Therefore, it is likely that NAP-1 is secreted by FDC in the NP and may play an immune modulatory role in NPC.
Highlights
Nasopharyngeal carcinoma (NPC) is an endemic cancer with high incidence in Southeast Asia and Southern China with obvious inclination toward racial and geographic influence
Sixteen of the 37 clusters contained novel not previously annotated sequences. Among those we focused our attention on 4 expression sequence tags (EST) (BG222624 mapped chromosome to 5q, BG231276 mapped to 2p, BG231174 mapped to 3p and BG231197 mapped to 4q) located in chromosomal areas in which a high frequency of amplifications or deletions have been reported [4,5,6]
No differential expression between NPC and paired NP specimens could be observed by reverse transcription (RT)-PCR for three ESTs (BG222624, BG231276, BG231174) while differences were noted for the one mapped on chromosome 4q
Summary
Nasopharyngeal carcinoma (NPC) is an endemic cancer with high incidence in Southeast Asia and Southern China with obvious inclination toward racial and geographic influence. Journal of Translational Medicine 2004, 2 http://www.translational-medicine.com/content/2/1/10 suppressor genes such as p53 and p16 have been described [2] To these days there is no conclusive molecular understanding of the pathogenesis of NPC and the quest for relevant associations between gene expression patterns in this disease remains relevant. Traditional cDNA library screening can subsequently offer the opportunity to expand knowledge on the identified genes by utilizing information collected from various data bases We utilized this Human Genome Searching Method combined with nested PCR to extend available sequence information on genes of putative interest with particular focus on the characterization of the 5' end and/or the full length of available cDNA libraries [3]. The gene was named nasopharyngeal carcinoma-associated peptide (NAP)-1 and characterization of its pattern of expression in normal and cancerous tissues was undertaken
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