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

我们在肿瘤细胞系中进行了基于同源框基因突变的肿瘤发生机制的分析。我们选择了人乳头瘤病毒感染致癌所致的宫颈癌作为模型。应用DNA微阵列技术对几种宫颈癌细胞株进行了HPV基因分型。寻找27种HPV型基因对宫颈癌细胞株(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).的感染宫颈癌细胞株的HPV基因分型如下：Hela：HPV 18型，Hela S3：HPV 18型，ME 180：HPV阴性，Caski：HPV 16型，SKG IIIa：HPV 16型，SKG IIIb HPV 16型，Boku HPV 16型，KF HPV阴性。HPV16型和18型在宫颈癌中被认为是致癌病毒类型。我们制备了HPV16型的反向引物(MY11：CC GTT ATG TCC CTG TGC，GP6+：TG ATT TAC AGT TTA TTT TTC)，通过反向聚合酶链式反应检测了感染HPV16的癌细胞中HPV16的序列，并对未检测到的癌细胞基因组序列进行了扩增。同时，我们还进行了DNA芯片分析，以检测癌细胞中的癌基因、转移基因和多药耐药基因，为开发分子靶向药物奠定了基础。我们确定了具有多药耐药功能的两个新基因：tbce和CITED2。

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.