Development of Molecular Targeting Agents Based on Analysis Oncogenesis with Homeobox Gene Mutation

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We performed analysis of mechanisms of oncogenesis based on homeobox gene mutation in cancer cell lines. We selected cervical cancer caused of oncogenesis by the infection of human papilloma virus as the model. The HPV genotyping of several cervical cancer cell lines were studied with DNA microarray analysis. Twenty-seven HPV gene genotypes were searched for infection to cervical cancer cell lines (HPV-6,11,16,18,31,33,34,35,39,40,42,43,44,45,51,52,54,56,58,59,62,66,67,68,69,70,72). The HPV genotyping of cervical cancer cell lines as below ; Hela : HPV Type18, Hela S3 : HPV Type18, ME 180 : HPV Negative, Caski : HPV Type 16, SKG IIIa : HPV Type16, SKG IIIb HPV Type 16, Boku HPV Type 16, KF HPV Negative. HPV type 16 and type 18 are recognized as oncogenic virus type in cervical cancers. We prepared inversed primer of HPV type16(MY11 : CC GTT ATG TCC CTG TGC, GP6+ : TG ATT TAC AGT TTA TTT TTC), and performed Inverse PCR to detect the sequence of HPV 16 in cancer cell lines infected HPV 16 with amprifining the undetected sequence of genome of cancer cells.We also performed DNA microarray analysis to detect oncogeneic genes, metastatic genes, and multidrug resistant genes in cancer cell lines for developing molecular targeting agents. We determined the novel two genes, TBCE and CITED2, that have the functions as multidrug resistant genes.