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SORTING THROUGH THE MUC: A CHARACTERIZATION OF MUC1 IN ACQUIRED CHEMO-RESISTANCE IN NON-SMALL CELL LUNG CANCER

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Material Information

Title:
SORTING THROUGH THE MUC: A CHARACTERIZATION OF MUC1 IN ACQUIRED CHEMO-RESISTANCE IN NON-SMALL CELL LUNG CANCER
Physical Description:
Book
Language:
English
Creator:
Wells, Alexandria
Publisher:
New College of Florida
Place of Publication:
Sarasota, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Bachelor's ( B.A.)
Degree Grantor:
New College of Florida
Degree Divisions:
Natural Sciences
Area of Concentration:
Biology, Chemistry
Faculty Sponsor:
Clore, Amy

Subjects

Genre:
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, territorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
Related Apoptosis Inducing Ligand (TRAIL) in non-small cell lung cancer. The ability of cancer cells to gain resistance to chemotherapy treatments has been attributed to their ability to evade apoptosis initiated by ligands like TRAIL through the dysregulation of otherwise harmless proteins, such as MUC1. A decrease in catalase expression, coupled by an increase in the presence of reactive oxygen species in TRAIL-resistant cells, partially accounts for the overexpression of MUC1. However, the pathway leading to MUC1 overexpression has not been fully elucidated, and the proteins with which MUC1 associates in order to disrupt TRAIL signaling within the cell are not all known. Two TRAIL-resistant non-small cell lung cancer cell lines, A549 and H460, were established to study MUC1’s role in acquired chemo-resistance. The levels at which MUC1 and catalase are regulated were examined and possible mechanisms responsible for this regulation explored. MUC1 and catalase were both regulated at either the transcriptional or post-transcriptional level, suggesting a potential role for miRNA regulation of these genes. Three candidates potentially responsible for this regulation, miRNA 943, miRNA 146a, and miRNA 551b, were tested for their expression in non-resistant and TRAIL-resistant cells. Only miRNA 551b was found to be upregulated in A549 TRAIL-resistant cells, but not in H460 TRAIL-resistant cells. To further investigate its role in catalase regulation, levels of miRNA 551b were ‘knocked down’ (reduced), and MUC1 and catalase levels observed. Transient knockdown of miRNA 551b in A549 TRAIL-resistant cells did not conclusively lead to recovery of catalase levels, and MUC1 remained overexpressed. It was concluded that while MUC1 and catalase are regulated prior to translation, miRNA 551b may not be responsible for this regulation. MUC1 transient knockdown was used to observe the effect on various pro-survival proteins, including phosphorylated epithelial growth factor receptor (pEGFR), unphosphorylated EGFR, phosphorylated protein kinase B (pAkt), cellular FADD-Like Interleukin-1β-Converting Enzyme Inhibitory Protein (c-FLIP), cyclooxygenase-2 (COX-2), and Myeloid cell leukemia sequence 1 (Mcl-1). MUC1 knockdown in A549 TRAIL-resistant cells potentially attenuated expression of MUC1 and c-FLIP, but not pEGFR, EGFR, pAkt, COX-2 or Mcl-1. Based on these results, MUC1 appears to potentially be involved in the regulation of c-FLIP, a well-established pro-survival protein involved in the termination of TRAIL signaling, suggesting a possible pathway for inhibition of apoptosis in chemo-resistant cells.
Statement of Responsibility:
by Alexandria Wells
Thesis:
Thesis (B.A.) -- New College of Florida, 2014
General Note:
RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE
Bibliography:
Includes bibliographical references.
General Note:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
General Note:
Faculty Sponsor: Clore, Amy

Record Information

Source Institution:
New College of Florida
Holding Location:
New College of Florida
Rights Management:
Applicable rights reserved.
Classification:
S.T. 2014 W455
System ID:
AA00024829:00001

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