Proteomic comparison of nasopharyngeal cancer cell lines C666-1 and NP69 identifies down-regulation of annexin II and beta2-tubulin for nasopharyngeal carcinoma.
BACKGROUND
Nasopharyngeal carcinoma (NPC), common in southern China and North Africa, has a complex etiology involving interplay between viral, environmental, and hereditary factors and is almost constantly associated with the Epstein-Barr virus. Since the prognosis of locally advanced and metastatic diseases is poor, increased understanding of the pathogenesis of NPC would be important for discovering novel markers for patients' management.


OBJECTIVE
To compare the proteomic expression profile between an Epstein-Barr virus-associated NPC cell line (C666-1) and a normal NP cell line (NP69). The proteins with differential expression were analyzed in 40 undifferentiated NPC paraffin-embedded specimens.


METHODS
Differentially expressed proteins discovered between the two cell lines were identified by mass spectrometry. After confirmation by immunocytochemical staining, their expression in patient samples was measured using 40 pairs of undifferentiated NPCs together with their adjacent normal epithelia.


RESULTS
Proteomic findings indicated that adenosine triphosphate synthase alpha chain was up-regulated, whereas annexin II, annexin V, beta(2)-tubulin, and profilin 1 were down-regulated. After confirming the results in agar-processed cell lines, annexin II and beta(2)-tubulin expression were found to be lower in tumor cells than in adjacent normal epithelial cells in 100% and 90% of the patients' specimens, respectively. Finally, annexin II down-regulation was positively associated with lymph node metastasis, suggesting that it may be a prognostic factor in NPC.


CONCLUSIONS
The results suggest that annexin II and beta(2)-tubulin down-regulation is important in NPC formation and may represent potential targets for further investigations.
Chan
Charles M L
CM
Department of Clinical Oncology, Sir Y. K. Pao Centre for Cancer, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.
Wong
S C Cesar
SC
Lam
Money Y Y
MY
Hui
Edwin P
EP
Chan
John K C
JK
Lo
Elena S F
ES
Cheuk
W
W
Wong
Manson C K
MC
Tsao
S W
SW
Chan
Anthony T C
AT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051304:Profilins / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D016601:RNA-Binding Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
D017306:Annexin A2; D017304:Annexin A5; D014408:Biomarkers, Tumor; D051304:Profilins; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D014404:Tubulin; C067169:RPL22 protein, human