Identification of differentially expressed genes in oral squamous cell carcinoma.
Rapid advances in multimodality therapy have not significantly improved the overall 5-yr survival of oral cancer patients in the past two decades, thereby underscoring the need for molecular therapeutics. The development of new treatment strategies for more effective management of oral cancer requires identification of novel biological targets. Therefore, the aim of this study was to identify novel genes associated with oral tumorigenesis by comparing gene expression profile of oral squamous cell carcinomas (OSCCs) and matched nonmalignant oral epithelial tissues with differential display. Of the 180 differentially expressed cDNAs isolated, reamplified, and cloned into pGEMT-Easy Vector, 26 cDNAs were confirmed to be upregulated in OSCCs by reverse Northern blot analysis. The differentially expressed genes included components of immune system, signaling pathways, angiogenesis, cell structure, proliferation, apoptosis, cell-adhesion, and cellular metabolism. Reverse transcription (RT)-polymerase chain reaction (PCR) analysis of 15 OSCCs and matched nonmalignant oral tissues provided the first evidence that 14-3-3-zeta, melanoma metastasizing clone D (MEMD), KIAA0471, sperm protein 17 (SP17), TC21, and anti-TNF alpha antibody are upregulated in OSCCs. Immunohistochemical analysis confirmed overexpression of 14-3-3-zeta and TC21 protein, a member of the Ras family, in OSCCs as compared to histologically normal oral tissues validating the differential display analysis. Identification of six novel differentially expressed genes in oral tumors adds to the repertoire of genes associated with oral carcinogenesis and provides candidate potential biological targets for diagnosis and/or therapy. Further characterization of the 14 unknown differentially expressed cDNAs identified in this study may provide significant clues for understanding the molecular mechanisms underlying oral tumorigenesis.
Arora
Shilpi
S
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Matta
Ajay
A
Shukla
Nootan Kumar
NK
Deo
S V S
SV
Ralhan
Ranju
R
D048948:14-3-3 Proteins / Q000096:biosynthesis; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis; D020559:Monomeric GTP-Binding Proteins / Q000096:biosynthesis; D009061:Mouth Mucosa / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D009369:Neoplasms / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048348:Reverse Transcription; D015398:Signal Transduction; D012984:Software; D013997:Time Factors
D048948:14-3-3 Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; D012313:RNA; C087360:RRAS2 protein, human; D020559:Monomeric GTP-Binding Proteins