Ovarian Cancer Cell Line Models Research Articles

Characterization of the 3p12.3‐pcen region associated with tumor suppression in a novel ovarian cancer cell line model genetically modified by chromosome 3 fragment transfer

The genetic analysis of nontumorigenic radiation hybrids generated by transfer of chromosome 3 fragments into the tumorigenic OV-90 ovarian cancer cell line identified the 3p12.3-pcen region as a candidate tumor suppressor gene (TSG) locus. In the present study, polymorphic microsatellite repeat analysis of the hybrids further defined the 3p12.3-pcen interval to a 16.1 Mb common region containing 12 known or hypothetical genes: 3ptel-ROBO2-ROBO1-GBE1-CADM2-VGLL3-CHMP2B-POU1F1-HTR1F-CGGBP1-ZNF654-C3orf38-EPHA3-3pcen. Seven of these genes, ROBO1, GBE1, VGLL3, CHMP2B, CGGBP1, ZNF654, and C3orf38, exhibited gene expression in the hybrids, placing them as top TSG candidates for further analysis. The expression of all but one (VGLL3) of these genes was also detected in the parental OV-90 cell line. Mutations were not identified in a comparative sequence analysis of the predicted protein coding regions of these candidates in OV-90 and donor normal chromosome 3 contig. However, the nondeleterious sequence variants identified in the transcribed regions distinguished parent of origin alleles for ROBO1, VGLL3, CHMP2B, and CGGBP1 and cDNA sequencing of the hybrids revealed biallelic expression of these genes. Interestingly, underexpression of VGLL3 and ZNF654 were observed in malignant ovarian tumor samples as compared with primary cultures of normal ovarian surface epithelial cells or benign ovarian tumors, and this occurred regardless of allelic content of 3p12.3-pcen. The results taken together suggest that dysregulation of VGLL3 and/or ZNF654 expression may have affected pathways important in ovarian tumorigenesis which was offset by the transfer of chromosome 3 fragments in OV-90, a cell line hemizygous for 3p.

Reprogramming of the transcriptome in a novel chromosome 3 transfer tumor suppressor ovarian cancer cell line model affected molecular networks that are characteristic of ovarian cancer

Tumor suppression as a consequence of the transfer of chromosome 3p fragments was previously observed in a novel epithelial ovarian cancer (EOC) OV-90 cell line model harboring loss of 3p. Microarray analysis revealed that tumor suppression was associated with a modified transcriptome. To investigate the relevance of the altered transcriptome, the differentially expressed genes identified by Affymetrix analysis in the 3p transfer studies, were integrated with a comparative microarray analysis of normal ovarian surface epithelial (NOSE) cells and malignant ovarian (TOV) cancers. Data from 219 significantly differentially expressed genes exhibited patterns in the direction predicted by the analysis of 3p transfer study. The 30 genes with the highest statistically significant differences (P < 1 x 10(-8)) in expression were found consistently differentially expressed between NOSE and TOV samples. The investigation of these genes in benign serous ovarian tumors and EOC cell lines also exhibited predictable expression patterns. Within the group of differentially expressed genes were SPARC, DAB2, CP, EVI1, ELF3, and EHD2, known to play a role in ovarian cancer, genes implicated in other cancers, such as GREM1 and GLIPR1, as well as genes not previously reported in a cancer context such as AKAP2 and ATAD4. A number of the differentially expressed genes are implicated in the TGF-beta signaling pathway. These findings suggest that the reprogramming of the transcriptome that occurred as a consequence of the chromosome 3 transfer and tumor suppression affected molecular networks that are characteristic of ovarian carcinogenesis thus validating our novel ovarian cancer cell line model.

Combination of the heat shock protein 90 (HSP90) chaperone inhibitor 17-allylamino, 17-demethoxygeldanamycin (17AAG) and conventional cytotoxic agents in an ovarian cancer cell line model

Combination of the heat shock protein 90 (HSP90) chaperone inhibitor 17-allylamino, 17-demethoxygeldanamycin (17AAG) and conventional cytotoxic agents in an ovarian cancer cell line model