Investigating the role of SAMHD1 in response to Camptothecin and Sacituzumab Govitecan in triple-negative breast cancer cell line MDA-MB-231 Open Access

Abstract

Due to the lack of response to hormone therapy and therapies targeting human epidermal growth factor receptor 2 (HER2), triple-negative breast cancer (TNBC) patients need biomarkers to identify individual sensitivity to conventional treatments inducing DNA damage. Protein Sterile Alpha Motif and Histidine-Aspartic acid domain containing protein 1 (SAMHD1) was previously reported as biomarker for Camptothecin (CPT) and Poly (ADP- ribose) polymerase (PARP) inhibitor sensitivity in human osteosarcoma cell line, and it has a characterized role in facilitating homologous recombination (HR) mediated DNA double- strand break (DSB) repair. We hypothesized that loss of SAMHD1 might mediate sensitization of TNBC cell line to selected DNA damaging agents such as CPT and Sacituzumab Govitecan (SG). Interestingly, our present results show that loss of SAMHD1 does not sensitize MDA-MD-231 cells to DNA damaging agents CPT and SG as hypothesized. Additionally, we validated our findings by taking CtBP (C-terminal binding protein) interacting protein (CtIP) as a control and indeed observed a similar effect. Overall, our results reflect TNBC cell lines might mediate chemoresistance to SG and CPT upon SAMHD1 and CtIP depletion by activating other DNA repair pathways. 

Table of Contents

Introduction................................................................................................................................1 Results........................................................................................................................................5

Effect of Camptothecin (CPT) on MDA-MB-231 cell viability ............................................5

Loss of SAMHD1 produces no synergistic effect with CPT in MDA-MB-231 cell line ......6

Effect of Sacituzumab Govitecan (SG) on MDA-MB-231 cell viability...............................7

Loss of SAMHD1 produces no synergistic effect with SG in MDA-MB-231 cell line ........8

Loss of CtIP and SAMHD1 produces no synergistic effect with CPT and SG.....................9

Discussion ................................................................................................................................12

Materials and Methods.............................................................................................................15

Reference .................................................................................................................................18 

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Cell Biology, Genetics
Keyword	DNA Repair Triple-negative Breast Cancer
Committee Chair / Thesis Advisor	David Yu, Emory University
Committee Members	Aparna Kesarwala, Emory University Roger Deal, Emory University Alexandre Orthwein, Emory University

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