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MOLECULAR MECHANISMS OF CHEMORESISTANCE IN
BREAST CANCER
by
Minal Chandravadan Patel
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
December 2008
Copyright 2008 Minal Chandravadan Patel
Object Description
| Title | Molecular mechanisms of chemoresistance in breast cancer |
| Author | Patel, Minal Chandravadan |
| Author email | minal226@gmail.com; minalcpa@usc.edu |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2008-08-20 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-10-15 |
| Advisor (committee chair) | Lee, Amy S. |
| Advisor (committee member) |
Cote, Richard Tokes, Zoltan A. |
| Abstract | Resistance to chemotherapy represents a major obstacle in breast cancer treatment. GRP78 is a protein upregulated in malignant but not benign human breast tumors, and is associated with resistance to chemotherapy in breast cancer patients. While it has been shown that this resistance depends on the BH3-only protein BIK, the mechanism of interaction between GRP78 and BIK still remains to be elucidated. Investigating the nature of this interaction, we discovered that deletion of the BH3-only domain in BIK results in altered protein interactions in 293T cells. Characterization of MCF-7/BUS human breast cancer cell clones that were resistant to estrogen-starvation therapy showed markedly elevated levels of GRP94. Knockdown of GRP94 by small interfering RNA in these resistant clones led to an increase in cell death. Resistance to chemotherapy is also a characteristic of cancer stem cells so we characterized molecular markers of putative breast cancer stem cells. Our results showed a minor putative breast cancer stem cell population in lymph node occult micrometastases. Overall these results help elucidate molecular characteristics that contribute to chemoresistance and that may serve as valuable targets for therapy, as well as help delineate molecular mechanisms contributing to estrogen-starvation therapy resistance in breast cancer. |
| Keyword | breast cancer; drug resistance; GRP78; GRP94; stem cells; stress |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m1670 |
| Contributing entity | University of Southern California |
| Rights | Patel, Minal Chandravadan |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@dots.usc.edu |
| Filename | etd-Patel-2414 |
| Archival file | uscthesesreloadpub_Volume29/etd-Patel-2414.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | MOLECULAR MECHANISMS OF CHEMORESISTANCE IN BREAST CANCER by Minal Chandravadan Patel A Thesis Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (BIOCHEMISTRY AND MOLECULAR BIOLOGY) December 2008 Copyright 2008 Minal Chandravadan Patel |
