Presentation Title

Gene regulatory pathways that modulate response to Dexamethasone and Daunorubicin in breast cancer cell lines

Faculty Mentor

Rheem Medh

Start Date

18-11-2017 2:15 PM

End Date

18-11-2017 3:15 PM

Location

BSC-Ursa Minor 54

Session

Poster 3

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Glucocorticoids (GCs) such as Dexamethasone (Dex) are anti-cancer agents that induce apoptosis through regulation of pro- and anti-apoptotic genes such as E4BP4, FOXO3A, BIM and BIRC3. Anthracyclines, such as Daunorubicin (Dauno) are effective anti-cancer agents for leukemias, breast cancer and ovarian cancer. E4BP4, a transcriptional regulator, is upregulated by GCs and mediates Dex-evoked apoptosis in leukemia cells, but is implicated as a survival factor in breast cancer. We hypothesize that E4BP4 regulation and its crosstalk with other pathways modulate either pro-survival or pro-apoptosis responses to chemotherapeutic agents. We are investigating the response of the triple negative breast cancer cell line MDA-MB-468 to Dex and Dauno (single agent and in combination) with respect to cell viability, apoptosis and regulation of pro- and anti-apoptotic genes. MTT cell viability assays determined that MDA-MB-468 cells are resistant to 1µM Dex, and sensitive to 50 nM Dauno. Cells are stained with Annexin V-FITC followed by epifluorescence microscopy to detect apoptotic cells. Evaluation of Dex and Dauno-mediated regulation of gene expression was done via reverse-transcriptase and end-point PCR analysis, followed by ImageJ quantitation, or by RT-qPCR analysis. Our data suggest that Dauno upregulates while Dex downregulates E4BP4 in MDA-MB-468 cells. Combined treatment significantly enhances FOXO3 upregulation compared to either single agent, in correlation with increased cell death. Our data suggest that Dex and Dauno may cooperatively promote apoptosis in MDA-MB-468 cells, and that E4BP4 expression correlates with cell death.

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Nov 18th, 2:15 PM Nov 18th, 3:15 PM

Gene regulatory pathways that modulate response to Dexamethasone and Daunorubicin in breast cancer cell lines

BSC-Ursa Minor 54

Glucocorticoids (GCs) such as Dexamethasone (Dex) are anti-cancer agents that induce apoptosis through regulation of pro- and anti-apoptotic genes such as E4BP4, FOXO3A, BIM and BIRC3. Anthracyclines, such as Daunorubicin (Dauno) are effective anti-cancer agents for leukemias, breast cancer and ovarian cancer. E4BP4, a transcriptional regulator, is upregulated by GCs and mediates Dex-evoked apoptosis in leukemia cells, but is implicated as a survival factor in breast cancer. We hypothesize that E4BP4 regulation and its crosstalk with other pathways modulate either pro-survival or pro-apoptosis responses to chemotherapeutic agents. We are investigating the response of the triple negative breast cancer cell line MDA-MB-468 to Dex and Dauno (single agent and in combination) with respect to cell viability, apoptosis and regulation of pro- and anti-apoptotic genes. MTT cell viability assays determined that MDA-MB-468 cells are resistant to 1µM Dex, and sensitive to 50 nM Dauno. Cells are stained with Annexin V-FITC followed by epifluorescence microscopy to detect apoptotic cells. Evaluation of Dex and Dauno-mediated regulation of gene expression was done via reverse-transcriptase and end-point PCR analysis, followed by ImageJ quantitation, or by RT-qPCR analysis. Our data suggest that Dauno upregulates while Dex downregulates E4BP4 in MDA-MB-468 cells. Combined treatment significantly enhances FOXO3 upregulation compared to either single agent, in correlation with increased cell death. Our data suggest that Dex and Dauno may cooperatively promote apoptosis in MDA-MB-468 cells, and that E4BP4 expression correlates with cell death.