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Expression profiles of 290 ESTs mapped to chromosome 3 in human epithelial ovarian cancer cell lines using DNA
Emily N Manderson1, Anne-Marie Mes-Masson, Jaroslav Novak
1Department of Human Genetics, McGill University, Montreal, Quebec H3A 1B1, Canada.
Abstract:
We have investigated previously the utility of oligonucleotide expression microarray technology in an analysis of four spontaneously transformed epithelial ovarian cancer (EOC) cell lines, TOV-21G, TOV-81D, OV-90, and TOV-112D. Here, we examine the expression of 290 expressed sequence tags (ESTs) that map to human chromosome 3 in a primary culture derived from normal ovarian surface epithelium (NOSE), NOV-31, and the four spontaneously transformed EOC cell lines. One of these cell lines, OV-90, harbors a deletion of an entire chromosome 3p arm. Whereas the most aggressive cell lines (OV-90, TOV-112D, and TOV-21G) exhibited the highest levels of expression, assessed by the mean of expression values of all ESTs, OV-90 showed the lowest mean of expression of ESTs that map to the 3p arm in comparison with TOV-112D and TOV-21G. This difference in expression profile of 3p ESTs in OV-90 is also reflected in the ratio of expression of ESTs on 3p versus the 3q arm and in that the expression values of ESTs that map to 3p were more often lower than higher in OV-90 in two-way comparisons with NOV-31, TOV-21G, and TOV-112D. The loss of a 3p arm does not affect the pattern of differential expression in analyses based on the range of numeric expression values of each EST or fold differences in expression for each EST in comparison with NOV-31. However, 25 differentially expressed ESTs were identified on the basis of threefold differences in expression values between NOV-31 and any EOC cell line; and six of these ESTs were differentially expressed uniquely in OV-90. The investigation of these ESTs could facilitate the identification of novel chromosome 3 genes implicated in ovarian tumorigenesis.
Insights
This study analyzed chromosome 3 gene expression in ovarian cancer cell lines. Specific 3p arm expression differences were found in OV-90, potentially identifying novel ovarian cancer genes.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Oncology
Background:
- Ovarian cancer is a significant health concern, with understanding gene expression crucial for diagnosis and treatment.
- Oligonucleotide expression microarray technology has been used to analyze gene expression patterns in cancer.
- Human chromosome 3 contains genes that may play a role in ovarian tumorigenesis.
Purpose of the Study:
- To examine the expression of 290 expressed sequence tags (ESTs) mapping to human chromosome 3 in normal ovarian surface epithelium and ovarian cancer cell lines.
- To investigate differential gene expression patterns associated with ovarian cancer, particularly in cell lines with chromosomal abnormalities.
- To identify novel genes on chromosome 3 implicated in ovarian tumorigenesis.
Main Methods:
- Utilized oligonucleotide expression microarray technology to analyze gene expression profiles.
- Compared expression levels of 290 ESTs mapping to chromosome 3 across normal ovarian surface epithelium (NOV-31) and four ovarian cancer cell lines (TOV-21G, TOV-81D, OV-90, TOV-112D).
- Analyzed expression data based on mean expression values, ratios of 3p/3q arm expression, and fold differences, focusing on cell line OV-90 with a 3p arm deletion.
Main Results:
- Most aggressive ovarian cancer cell lines showed higher overall EST expression, but OV-90 exhibited lower mean expression of 3p arm ESTs compared to other cell lines.
- The expression profile of 3p ESTs in OV-90 differed significantly, reflected in 3p/3q arm ratios and lower expression values in two-way comparisons.
- Identified 25 differentially expressed ESTs based on threefold differences between normal and cancer cells, with six ESTs uniquely differentially expressed in OV-90.
Conclusions:
- Specific differences in chromosome 3 gene expression, particularly on the 3p arm, are associated with ovarian cancer cell lines.
- The unique expression profile in OV-90, despite a 3p arm deletion, provides insights into chromosome 3's role in ovarian tumorigenesis.
- Further investigation of the identified differentially expressed ESTs may lead to the discovery of novel genes involved in ovarian cancer development.
