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

我们在癌细胞系中进行了基于同源异型盒基因突变的肿瘤发生机制的分析。我们选择人乳头瘤病毒感染致宫颈癌的模型。应用基因芯片技术对几种宫颈癌细胞株进行HPV基因分型研究。检索27种HPV基因型（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）对宫颈癌细胞系的感染情况。宫颈癌细胞系的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。HPV 16型和18型被认为是宫颈癌的致癌病毒类型。我们制备了HPV 16型反向引物，（MY11：CC GTT ATG TCC CTG TGC，GP6+：TG ATT TAC AGT TTA TTT TTC），采用反向PCR技术检测感染HPV 16的癌细胞株中HPV 16的基因序列，扩增癌细胞基因组中未检测到的序列，并采用基因芯片技术检测癌基因、转移基因、和癌细胞系中的多药耐药基因，用于开发分子靶向剂。我们确定了两个新的基因，TBCE和CITED 2，具有多药耐药基因的功能。

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.