Type of Document Master's Thesis Author Robinson, Rose Marie URN etd-101198-121758 Title Microphysiometry Studies of Rapid Binding of Insulin-Like Growth Factor I by Parental and Transfected Mammary Epithelial Cell Lines Degree Master of Science Department Chemical Engineering Advisory Committee
Advisor Name Title Forsten-Williams, Kimberly Committee Chair Akers, Robert Michael Committee Member Davis, Richey M. Committee Member Keywords
- Insulin-Like Growth Factor II (IGF-II)
- Insulin-Like Growth Factor I (IGF-I)
Date of Defense 1998-10-16 Availability unrestricted Abstract
Breast cancer is a leading cause of cancer death of women in the U.S. today. Members of the family of insulin-like growth factors (IGFs) are proposed to play a major role in the development and subsequent uncontrolled proliferation of breast cancer cells. Insulin-like growth factor-I (IGF-I) is known to be a potent mitogen for mammary epithelial cells. IGF-I acts by binding to cell surface receptors, thereby stimulating a cascade of events leading to cell division. In the interest of interrupting the effect of IGF-I on cancerous mammary epithelial cells, an understanding of how IGF-I behaves in the presence of other extracellular components is needed. This study examines the IGF-I response of SV40-IGF-I, an immortalized bovine mammary epithelial cell line which secretes IGF-I constitutively.
The microphysiometer allows real-time sampling of cellular activity by measuring the excretion of protons from a sample of cells stimulated by IGF-I binding. The contributions of other factors in enhancing or suppressing stimulation can be compared by examining the pH response of cells exposed to IGF-I in the presence of these factors. We present data showing the stimulatory effect of IGF-I in a dose dependent manner on the SV40-IGF-I cell line.
In addition, we compare IGF-I stimulation with stimulation by long R3IGF-I, a substituted analogue of IGF-I having a reduced binding affinity for the IGF binding proteins. We examine the effect of insulin-like binding protein-3 (IGFBP-3) both in the presence and absence of IGF-I, finding no IGF-I independent effect in the rapid binding experiment and no effect on stimulation of IGFBP-3 pre-incubated cells by subsequent IGF-I challenge. This is of particular interest due to recent work demonstrating an IGF-independent IGFBP-3 response in a number of cell lines. Binding studies to correlate with the rapid binding stimulation show binding of the IGFBP-3 molecule with high affinity to a small number of surface receptors on the SV40-IGF-I cell.
Analysis of the extracellular environment and the components contributing to the binding of IGF-I to the cell membrane receptor will provide information for the development of interventions to slow or interrupt the process of IGF-I binding and therefore cancer growth. Optimization of the Cytosensor(r) Microphysiometer System for the (transfected) SV40-IGF-I and the (parental) MAC-T cell lines was achieved to continue comparison studies of autocrine and paracrine stimulation of bovine mammary epithelial cells by IGF-I.
This work was supported by the Whitaker Foundation Biomedical Engineering Grant.
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28.8 Modem 56K Modem ISDN (64 Kb) ISDN (128 Kb) Higher-speed Access Abstract.pdf 5.03 Kb 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 ACKn_DOC.pdf 7.88 Kb 00:00:02 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 Appendix_A.pdf 3.26 Kb < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 Bibliography.pdf 16.18 Kb 00:00:04 00:00:02 00:00:02 00:00:01 < 00:00:01 Chapter1.pdf 282.32 Kb 00:01:18 00:00:40 00:00:35 00:00:17 00:00:01 Chapter2.pdf 479.72 Kb 00:02:13 00:01:08 00:00:59 00:00:29 00:00:02 Chapter3.pdf 194.15 Kb 00:00:53 00:00:27 00:00:24 00:00:12 00:00:01 Chapter4.pdf 68.50 Kb 00:00:19 00:00:09 00:00:08 00:00:04 < 00:00:01 Chapter5.pdf 82.67 Kb 00:00:22 00:00:11 00:00:10 00:00:05 < 00:00:01 Chapter6.pdf 9.39 Kb 00:00:02 00:00:01 00:00:01 < 00:00:01 < 00:00:01 CONTENT_DOC.pdf 11.89 Kb 00:00:03 00:00:01 00:00:01 < 00:00:01 < 00:00:01 thesistitle.pdf 2.71 Kb < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 Vita.pdf 3.10 Kb < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01 < 00:00:01
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