Regulatory Networks in Breast Cancer Stem Cell Response to Selumetinib

Background: The mitogen-activated protein kinase (MAPK)signaling pathway has a role in cell proliferation and survival.The mitogen-activated protein kinase (MEK) activity is vitalfor MAPK signaling. So, targeting of MEK in malignant cellshave been done in many studies. Selumetinib drug is a non-ATP- competitive MEK inhibitor, has antitumor activity in varietyof different tumor type. Selumetinib in combination withchemotherapy drugs inhibit tumor growth and induce apoptosismore effective. Recently, many studies have been shown thatselumetinib inhibits cancer stem cell in breast cancer via affectMEK expression. According to these data, selumetinib can beuseful for treatment of cancer and reduce tumorigenic activity.Materials and Methods: In this study for getting differentgenes expression in MAPK pathways that were affected by selumetinibAfter ۴h and ۲۴ h, first we obtained the gene name listfor this study. Then gene ontology analyses were conducted tofind the most affected genes. Most important TFs were studiedand using all these knowledges a core regulatory network wasconstructed for comparison.Results: Our approach revealed many aspects of gene expression.We could correlate some of these differences to key regulatoryelements TFs. Network analysis uncovered major differencesin core regulatory network between these genes in variedpathways.Conclusion: These analyses would be useful for clinical application.We have identified that different genes don’t have thesame expression. We hope that our analysis facilitates selectionof the most appropriate genes for cancer therapy.

کلیدواژه ها:

Mitogen-Activated Protein Kinase (MAPK) ، Selumetinib ، Breast Cancer Stem Cells