New approaches to pathogenic gene function discovery with human squamous cell cervical carcinoma by gene ontology.
OBJECTIVE
This study utilized mRNA differential display and the Gene Ontology (GO) analysis to characterize the multiple interactions of a number of genes with gene expression profile involved in squamous cell cervical carcinoma.


METHODS
mRNA differential displays were used to identify potential transcripts that were differentially expressed between cervix cancers of 13 patients (invasive cancer stages Ib-IIb) and universal reference RNAs comprised of 17 different normal cervixes. Aberrant bands were excised and used to make cDNA, which was sequenced. DNA sequences were compared to other nucleic acids in the NCBR database for homology. Transcript expression was verified in select samples using RT-PCR and North blotting. The specific functions were correlated with gene expression patterns via gene ontology.


RESULTS
Fifty-eight genes were up- or down-regulated above 2-fold and organized into reciprocally dependent sub-function sets depending on the cervical cancer pathway. The GO analysis showed that squamous cell cervical carcinogenesis underwent complete up-regulation of cell cycle, transport, epidermal differentiation, protein biosynthesis, and RNA metabolism. Also, genes belonging to protein metabolism and catabolism activity were significantly up-regulated. In contrast, significant down-regulation was shown in muscle development, cell adhesion, and damaged DNA binding activity.


CONCLUSIONS
The GO analysis can overcome the complexity of the gene expression profile of the squamous cell cervical carcinoma-associated pathway and identify several cancer-specific cellular processes as well as genes of unknown function. Also, GO analysis can serve as a powerful basis for a molecular classification of carcinogenesis.
Seo
Min-Jae
MJ
Catholic Research Institutes of Medical Science, The Catholic University of Korea, Seoul, Korea.
Bae
Su Mi
SM
Kim
Yong-Wan
YW
Kim
Yong Wook
YW
Hur
Soo Young
SY
Ro
Duck Young
DY
Lee
Joon Mo
JM
Namkoong
Sung Eun
SE
Kim
Chong Kook
CK
Ahn
Woong Shick
WS
D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex