Honors Theses and Capstones

Date of Award

Spring 2014

Project Type

Senior Honors Thesis

College or School

COLSA

Department

Biological Sciences

Program or Major

Biomedical Science: MVS Option

Degree Name

Bachelor of Science

First Advisor

David Townson

Abstract

Survival of cancer cells is influenced by a variety of factors, including physical elements such as keratin filaments. We know HeLa cells containing or lacking keratin 8/18 intermediate filaments (K+ and K- cells, respectively) are more sensitive to the death-inducing effects of Fas agonist compared to the cytokines tumor necrosis factor alpha (TNF-α) or TNF-related apoptosis-inducing ligand. Additionally, K- cells are more sensitive to Fas-induced death than K+ as shown by previous studies using mitochondrial activity and caspase activation assays. In the current study we tested the hypothesis that keratin filaments associate with the mitogen activated protein kinase (MAPK) cascade to protect cells from Fas-induced death. To do this, K+ and K- cells were exposed to Fas agonist in the absence or presence of human epidermal growth factor (EGF) (known to stimulate MAPK) and then downstream phosphorylation of extracellular signal-regulated kinase (pERK) was measured. Fas agonist reduced pERK expression in both cell types (~32% less pERK compared to non-EGF-treated controls, n= 3 expts.). Conversely, EGF (50ng/ml) reversed this outcome, but again did so equally in K+ and K- cells. Intriguingly, K- cells were more responsive to EGF stimulation alone than K+ cells, regardless of EGF dose (pERK ~27% higher in K- than K+ cells, n= 3 expts.). The results suggest keratin 8/18 filaments do associate with the MAPK cascade to influence cell survival. Supported by the Hamel Center for Undergraduate Research (AB) and the COLSA Karabelas Fund (DHT).

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