Persistent Link:
http://hdl.handle.net/10150/626139
Title:
Mechanism of Action of ERBB Decoy Cancer Therapeutic Peptide SAH5
Author:
Makhani, Kiran
Issue Date:
2017
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Breast cancer is the most prevalent type of cancer and second leading cause of death in women. Among others, the triple negative breast cancer (TNBC) is the most invasive as it has the highest recurrence and death rates with no targeted therapeutic available thus far. Epidermal Growth Factor Receptor (EGFR) is one of the important targets as more than fifty percent of the TNBC overexpress it but all the therapies designed against it have failed to show significant results. The juxtamembrane domain of EGFR has been explored comparatively recently and has been used to design a decoy peptide with the anticipation to affect the EGFR downstream functions. Previous research has shown it to cause cell death in cancer cells. This study is aimed towards deciphering the mechanism of action of the stapled form of this decoy peptide-SAH5. It presents evidence that the peptide leads to an immediate intracellular calcium release from the Inositol 1,4,5 triphosphate on the endoplasmic reticulum, an inhibition of which can rescue SAH5 induced cell death. The study also demonstrate that the peptide is able to increase the production of Reactive Oxygen Species (ROS) in mitochondria, part of which is triggered by the peptide-induced calcium release.
Type:
text; Electronic Thesis
Keywords:
Breast cancer; Calcium; ERBB decoy peptide; IP3R; Reactive oxygen species
Degree Name:
M.S.
Degree Level:
masters
Degree Program:
Graduate College; Cellular and Molecular Medicine
Degree Grantor:
University of Arizona
Advisor:
Schroeder, Joyce A.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleMechanism of Action of ERBB Decoy Cancer Therapeutic Peptide SAH5en_US
dc.creatorMakhani, Kiranen
dc.contributor.authorMakhani, Kiranen
dc.date.issued2017-
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.description.abstractBreast cancer is the most prevalent type of cancer and second leading cause of death in women. Among others, the triple negative breast cancer (TNBC) is the most invasive as it has the highest recurrence and death rates with no targeted therapeutic available thus far. Epidermal Growth Factor Receptor (EGFR) is one of the important targets as more than fifty percent of the TNBC overexpress it but all the therapies designed against it have failed to show significant results. The juxtamembrane domain of EGFR has been explored comparatively recently and has been used to design a decoy peptide with the anticipation to affect the EGFR downstream functions. Previous research has shown it to cause cell death in cancer cells. This study is aimed towards deciphering the mechanism of action of the stapled form of this decoy peptide-SAH5. It presents evidence that the peptide leads to an immediate intracellular calcium release from the Inositol 1,4,5 triphosphate on the endoplasmic reticulum, an inhibition of which can rescue SAH5 induced cell death. The study also demonstrate that the peptide is able to increase the production of Reactive Oxygen Species (ROS) in mitochondria, part of which is triggered by the peptide-induced calcium release.en
dc.typetexten
dc.typeElectronic Thesisen
dc.subjectBreast canceren
dc.subjectCalciumen
dc.subjectERBB decoy peptideen
dc.subjectIP3Ren
dc.subjectReactive oxygen speciesen
thesis.degree.nameM.S.en
thesis.degree.levelmastersen
thesis.degree.disciplineGraduate Collegeen
thesis.degree.disciplineCellular and Molecular Medicineen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorSchroeder, Joyce A.en
dc.contributor.committeememberSchroeder, Joyce A.en
dc.contributor.committeememberLantz, Robert C.en
dc.contributor.committeememberMcEvoy, Justina D.en
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