Agonist binding of herg K+ channels inhibits epithelial cell extrusion but not apoptosis in MDCK monolayers; providing possibilities to cancer metastasis regulation

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Publication Type thesis
School or College College of Engineering
Department Biomedical Engineering
Faculty Mentor Jody Rosenblatt
Creator Loftus, Patrick D.
Title Agonist binding of herg K+ channels inhibits epithelial cell extrusion but not apoptosis in MDCK monolayers; providing possibilities to cancer metastasis regulation
Year graduated 2012
Date 2012-01
Description Metastasis is commonly referred to as cancerous cell movement from an original site to one or more sites elsewhere in the body. When these moving cancerous cells are malignant, an individual's chance of survival is decreased. In order for epithelial cells to move they are detached from the epithelium in a process called extrusion. By regulating this extrusion pathway it may be possible to regulate metastasis as well. Unfortunately, compared to the amount of knowledge about apoptosis, or programmed cell death, very little is known about the signals that regulate extrusion. One possible target of extrusionsignaling regulation is HERG K+ Channels, It is hypothesized that HERG channels will prevent extrusion but not apoptosis, thus providing a means of extrusion regulation while still allowing for apoptotic death targeting of tumors. MDCK monolayers were treated with HERG antagonists, MK499 and E-4031, as well as an agonist, PD-118057 and exposed to UV irradiation to induce apoptosis and extrusion. For the first time, we show that increasing the conductivity of HERG inhibits extrusion but not apoptosis. This result provides possibilities of • future strategies for tumor metastasis regulation that have currently been unexplored. These possibilities are very promising because many tumors over express HERG K+ channels that contain a beta isoform, her gib, different from healthy tissues.
Type Text
Publisher University of Utah
Subject Biomedical Engineering
Language eng
Rights Management (c) Patrick D. Loftus
Format Medium application/pdf
Format Extent 667,506 bytes
Permissions Reference URL https://collections.lib.utah.edu/details?id=1278297
ARK ark:/87278/s6x09h9j
Setname ir_htoa
Date Created 2016-11-01
Date Modified 2019-07-10
ID 205874
Reference URL https://collections.lib.utah.edu/ark:/87278/s6x09h9j
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