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Development of an insturmal method to evaluate insulin receptors and insulin-like growth factor-1 receptors homodimers and hybrid receptors in breast cancer

dc.contributor.authorShebani, Karima Ali, author
dc.contributor.authorRoess, Deborah A., advisor
dc.contributor.authorRoess, Deborah A., committee member
dc.contributor.authorBarisas, George B., committee member
dc.contributor.authorMiller, Charles W., committee member
dc.date.accessioned2016-08-18T23:11:39Z
dc.date.available2016-08-18T23:11:39Z
dc.date.issued2016
dc.description.abstractBreast cancer is a major public health problem in the United States and many other parts of the world. It is the second most common cancer and second leading cause of cancer death among women in the US. Insulin receptors (IR) and insulin-like growth factor-1 receptors (IGF1R) are found in normal mammary gland cells where they are involved in normal development and differentiation of these cells. There is substantial clinical, epidemiological, and experimental evidence indicating that these receptors are also involved in initiation and progression of neoplasia of mammary gland cells. IR and IGF1R numbers are increased in breast cancers and raise the possibility that IR and IGF1R may have roles in the biology of these tumors. In this project, we have developed new methods to evaluate the presence of IR homodimers and hybrid receptors formed from IR and IGF1R monomers. In initial experiments we have used three cell lines of CHO that stably express IR-GFP. Using flow cytometry, we found that low expressing cells had ~ 62,000receptors/cell, moderately expressing cells had ~ 130,000receptors/cell, and high expressing cells had ~ 205,000 receptors/cell. We then used homo-transfer fluorescence resonance energy transfer (homo-FRET) methods to evaluate possible interactions between IR monomers in the IR homodimer or IR and IGF1R subunits in hybrid receptors. Our results suggest that IR exists as an apparent monomer in cells expressing low numbers of IR-GFP. In cell lines highly expressing IR-GFP, there are minimally dimers and higher order receptor oligomers present on the plasma membrane. These results suggest that when IR is highly expressed, as in the case in many breast cancers, the receptor is likely to be found as a IR homodimer rather than as a hybrid IR-IGF1R receptor. Further studies beyond the scope of this project will evaluate the effects of IGF1R expression on the formation of IR homodimers.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifier.urihttp://hdl.handle.net/10217/176773
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.titleDevelopment of an insturmal method to evaluate insulin receptors and insulin-like growth factor-1 receptors homodimers and hybrid receptors in breast cancer
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineCell and Molecular Biology
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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