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Author
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Haik Mkhikian
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Biochemistry and
Molecular Biology,
and Philosophy
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Haik Mkhikian believes his undergraduate research experience is the primary reason for his award of a National Institutes of Health (NIH) scholarship. Haik will graduate this spring with a double major in Biochemistry and Molecular Biology, and Philosophy. After graduation, he will research in a laboratory at NIH for a year as he submits applications for medical school. Haik credits his best learning experiences to his failed experiments, which forced him to think of new approaches to his research. He counsels students to seek challenges and not to settle for easy classes. In his free time, Haik reads Indian philosophy and plays basketball, ping pong, and hacky sack.
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Abstract
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E-cadherin is a membrane protein found on epithelial cells that is involved in intercellular binding. It has been reported that metastasis, the invasive stage of cancer, is often accompanied by decreased levels of E-cadherin. Furthermore, it is known that several substances can act as motility factors and promote the separation of cancer cells from each other and the main tumor, thereby promoting metastasis. We have already shown that normal breast tissue secretes such substances that increase motility in breast cancer cells. However, how these motility factors function and the pathways by which they cause cell separation remain unclear. We hypothesized that factors secreted by normal breast cells decrease E-cadherin levels in MCF-7 breast cancer cells, resulting in increased motility. We conducted E-cadherin staining, flow cytometry, and cell binding assays to test this hypothesis. We found that treating MCF-7 cells with normal breast cell secretions not only decreased the amount of E-cadherin staining exhibited by these cells and their ability to bind to other MCF-7 cells, but we also noted a 25% decrease in E-cadherin levels by flow cytometry. The findings showed a dose-dependent decrease in E-cadherin staining with a corresponding increase in motility. By further elucidating the mechanisms by which these motility factors act, we hope to create treatments that will inhibit their effects and thereby reduce cancer cell motility.
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Faculty
Mentor
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Philip M. Carpenter
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School of Medicine
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There is increasing understanding that tumor cells are not always aggressive solely because of their own characteristics. In many instances the normal tissues that surround tumor cells contribute to their behavior. Haik Mkhikian’s work is significant because it shows that normal breast cells can lead to one of the earliest steps of cancer spread—the separation of tumor cells from their surroundings. In this case, the separation is mediated by decreased expression of E-cadherin. In normal cells, E-cadherin acts as a “molecular glue” that keeps cells together. This work illustrates how the efforts of a dedicated student can lead to novel scientific findings.
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If
you wish to view the paper in its entirety, please select
the link given to the PDF file. [mkhikian.pdf]
If you wish to download the Adobe Acrobat Reader,
please go to Adobes website (www.adobe.com).
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© 2004
by the Regents of the University of California. All rights reserved.
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