Rouhimoghadam2018 - GPR30/PI3K/MAPK/STAT signaling pathway in normal and cancer cells
In the current study, we aimed to simulate the GPR30/PI3K/MAPK/STAT signaling pathway in normal and cancer cells by the use of ordinary differential equation modeling. In addition, we planned to show that MAPK activation pattern is different between normal and cancer models.
- Tamoxifen-Induced Apoptosis of MCF-7 Cells via GPR30/PI3K/MAPKs Interactions: Verification by ODE Modeling and RNA Sequencing.
- Rouhimoghadam M, Safarian S, Carroll JS, Sheibani N, Bidkhori G
- Frontiers in physiology , 1/ 2018 , Volume 9 , pages: 907 , PubMed ID: 30050469
- Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
- Tamoxifen (Nolvadex) is one of the most widely used and effective therapeutic agent for breast cancer. It benefits nearly 75% of patients with estrogen receptor (ER)-positive breast cancer that receive this drug. Its effectiveness is mainly attributed to its capacity to function as an ER antagonist, blocking estrogen binding sites on the receptor, and inhibiting the proliferative action of the receptor-hormone complex. Although, tamoxifen can induce apoptosis in breast cancer cells via upregulation of pro-apoptotic factors, it can also promote uterine hyperplasia in some women. Thus, tamoxifen as a multi-functional drug could have different effects on cells based on the utilization of effective concentrations or availability of specific co-factors. Evidence that tamoxifen functions as a GPR30 (G-Protein Coupled Receptor 30) agonist activating adenylyl cyclase and EGFR (Epidermal Growth Factor Receptor) intracellular signaling networks, provides yet another means of explaining the multi-functionality of tamoxifen. Here ordinary differential equation (ODE) modeling, RNA sequencing and real time qPCR analysis were utilized to establish the necessary data for gene network mapping of tamoxifen-stimulated MCF-7 cells, which express the endogenous ER and GPR30. The gene set enrichment analysis and pathway analysis approaches were used to categorize transcriptionally upregulated genes in biological processes. Of the 2,713 genes that were significantly upregulated following a 48 h incubation with 250 μM tamoxifen, most were categorized as either growth-related or pro-apoptotic intermediates that fit into the Tp53 and/or MAPK signaling pathways. Collectively, our results display that the effects of tamoxifen on the breast cancer MCF-7 cell line are mediated by the activation of important signaling pathways including Tp53 and MAPKs to induce apoptosis.
Submitter of this revision: Krishna Kumar Tiwari
Modellers: Krishna Kumar Tiwari
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|Rouhimoghadam2018.cps||COPASI 4.27(build 217) file for the model||837.73 KB||Preview | Download|
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- Model originally submitted by : Krishna Kumar Tiwari
- Submitted: Feb 25, 2020 5:07:20 PM
- Last Modified: Feb 25, 2020 5:07:20 PM