Using ovarian cancer cell line OV90 as a starting line, we have developed a series of lines individually resistant to 3 different drugs (cisplatin, doxorubicin and paclitaxel). Three independent clones for each resistant phenotype was obtained, giving us a total of 9 cell lines for comparison to the parental cells (3 cisplatin resistant clones OV90C, 3 doxorubicin resistant clones OV90D, and 3 paclitaxel resistant clones OV90P). We have used Illumina microarrays to analyze gene expression of these clones and have identified genes differentially expressed in the various drug resistance phenotypes. Interestingly, we have identified several genes that are common to several resistance types. For example, ABCB1 and GAGE genes were consistently elevated in resistant cells, while PRSS8 and MSMB1 were consistently downregulated. We are currently validating these and other candidate genes by quantitative RT-PCR in these cell lines. We are also validating these genes in patient tissues using RT-PCR and immunohistochemistry. Finally, we are investigating the functional roles of these genes in ovarian cancer drug resistance using a number of molecular and cell biology approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000396-02
Application #
7963964
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2009
Total Cost
$277,427
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Sherman-Baust, Cheryl A; Becker, Kevin G; Wood Iii, William H et al. (2011) Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin. J Ovarian Res 4:21
Dahiya, Neetu; Morin, Patrice J (2010) MicroRNAs in ovarian carcinomas. Endocr Relat Cancer 17:F77-89
Li, Jianghong; Chigurupati, Srinivasulu; Agarwal, Rachana et al. (2009) Possible angiogenic roles for claudin-4 in ovarian cancer. Cancer Biol Ther 8:1806-14
Morin, Patrice J (2008) Learning about ovarian tumorigenesis by watching Cables. Cancer Biol Ther 7:189-90