Test of signaling pathways in cervical cancer
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Posted On :
Jan-16-2012
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Article Word Count :
762
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In this poster, I would introduce a new article published in cancer research and I wanna to recommend a way to discovery the relationship between gene expression and cancer in vivo. Researchers in this article just gave an example and we could do more study in similar way in future.
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In this poster, I would introduce a new article published in cancer research and I wanna to recommend a way to discovery the relationship between gene expression and cancer in vivo. Researchers in this article just gave an example and we could do more study in similar way in future.
The article “Pathway-specific analysis of gene expression data identifies the PI3K/Akt pathway as a novel therapeutic target in cervical cancer” introduce a way called Gene Set Enrichment Analysis (GSEA) which is based on an article “Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles” published in the ) Proc. Natl. Acad. Sci. USA. The method can help us to tell the gene expression which is closely linked to a certain cancer from the genes which are not so important to that type of cancer. And the key gene in the priori defined set would be showed statistically significantly.
In this article, researchers did not use cancer cell lines. They used tumor biopsies from patients with cervical cancer. And they test the gene expression depend on the RNA level harvested from frozen fresh biopsies by using Trizol reagent. Researchers tested a set of signaling pathways including RAS signaling pathway, Hypoxia/HIF1/VEGF, NFKB/immune modulators, PI3K/PTEN/Akt/mTOR, and EGFR. Comparing PET-positive tumor to PET-negative tumor, researchers concluded that PI3K/Akt signaling pathway and PTEN signaling pathway are up-regulated significantly. To confirm the Akt activation, researchers test the p-akt signals in the cervical cancer biopsies by a tissue microarray. The results showed that “there is a statistically significant association between pAkt staining intensity and increased SUVmax on the pretreatment PET, implying that activation of Akt in cervical tumors is associated with increased glucose uptake in vivo (mean difference -10.9, p < 0.0001, DF 113).”
As lacking of a detailed analysis of the PI3K/Akt pathway in cervical cancer, researchers’ study in this article did provide some new information to us and this study is valuable because of testing the signaling pathways in vivo. Depending on the study, researchers found that pAkt expression is associated with tumor glucose uptake in vivo. Researchers used PI3K LY294002, a PI3K inhibitor, to observe the effect of blocking PI3K and found that up-take of FDG decreased. But FDG uptake also decrease in the cell lines which did not over-express or over-activate akt. It seems that that Akt is activated when cells are exposed to glucose or during glucose uptake. Researchers also found that there may be no basal Akt activation in certain cancer cell lines, and presence of glucose may lead to Akt activation and subsequent glucose uptake and that this effect is significantly reduced when PI3K is inhibited.
In conclusion, this article suggested a new way for us to study the signaling pathways in vivo. We always used western or other methods to study the kinases level or activation of kinases in cell lines. But the result can not represent the fact in vivo. We can learn some methods from this article.
First, we can test different signaling pathways, to some extent, in vivo and find the key signaling pathway to that cancer. And we also can use PET to test the condition of patients where the biopsies we get so that we can keep the step with the disease development and try to explain the phenomena which cell lines can not explain.
Reference:
[1]Julie K Schwarz et al. Pathway-specific analysis of gene expression data identifies the PI3K/Akt pathway as a novel therapeutic target in cervical cancer. Clin Cancer Res Published OnlineFirst January 10, 2012.
[2]Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S. & Mesirov, J. P. (2005) Proc. Natl. Acad. Sci. USA 102, 15545-15550.
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