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.
Quinn
Michael C J
MC
Department of Human Genetics, McGill University, Montréal, Canada.
Filali-Mouhim
Abdelali
A
Provencher
Diane M
DM
Mes-Masson
Anne-Marie
AM
Tonin
Patricia N
PN
D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger