Clones derived from in vivo growing of murine ovarian epithelial cancer cell line IG-10 exhibit different phenotypes for gene expression, tumorigenicity and immune response
MOLECULAR CANCER THERAPEUTICS(2007)
摘要
C12 Ovarian cancer is an aggressive disease of poor prognosis and is the fourth leading cause of death when detected at advanced stages. Due to lack of appropriate animal models, studies involving tumorigenicity, tumor immune response and tumor progression at the molecular level are limited. We have isolated many clones derived from in vivo growing of the murine ovarian epithelial cancer cell line IG-10 and found the clones displaying diverse phenotypes. Many clones were found to be deficient in multiple components of the MHC-I antigen presentation pathway, including TAP and MHC-1. Soft agarose cloning assays showed different degrees of anchorage-independent growth among clones. However, these observations did not completely correlate with clones’ tumorigenicity in the context of in vivo tumor growth, suggesting the possibility that contrasting intrinsic gene expression of tumor clones and their interaction with immune cells may play an important role in affecting tumorigenicity. To detect potential candidate genes, we carried out a genome-wide transcriptomic analysis by using a low density array mouse immune panel that contains 96 genes pertaining to cell cycling, cytokines, chemokines, etc. The genes that were expressed at different levels among clones included 7 genes (Ccl5, CD38, Col4a5, Cxcl10, IL-10, Nos2 and Socs1) potentially implicated in in vivo tumorigenicity and immune response. Thus, our animal cell model provides a useful tool in studying ovarian cancer tumorigenicity and its interaction with the immune system, as well as a source of novel therapeutic targets.
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关键词
epithelial,different phenotypes,gene expression,cancer
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