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Prostate cancer expression of vascular endothelial growth factor splice forms in hypoxia

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2015, BS, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
Hypoxia is known to be a characteristic of the inner tumor environment. In order to restore oxygen to the tumor, cancer cells will increase production of vascular endothelial growth factor (VEGF) which is necessary for angiogenesis and, therefore, tumor growth. VEGF is present in different splice forms, with the predominant in cancer cells being VEGF121 and VEGF165. These splice forms have distinct characteristics which allow for different patterns of blood vessel formation within the tumor. VEGF121 lacks the heparin binding domain that is present in VEGF165, and thus is capable of diffusing away from the site of origin through the extracellular matrix and recruiting larger, pre-existing blood vessels. VEGF165, however, can bind to the heparin in the extracellular matrix and is sequestered locally, allowing it to create more internal microvessels than VEGF121. VEGF121 has also been implicated in more aggressive, metastatic cancer types. We hypothesized that VEGF expression in prostate cancer cells would increase in response to hypoxic conditions, favoring the VEGF121 isoform. We examined VEGF splice form mRNA production in both LNCaP and PC3 cells, which are prostate cancer cell lines with different metastatic potentials. Our findings suggest that hypoxia does cause an increase in both splice forms relative to expression under normoxic conditions, with a greater increase in fold change observed for VEGF121. These results of elevated VEGF121 indicate an increase in the potential for angiogenic and metastatic prostate cancer growth. Overall this work highlights the role of the hypoxic tumor microenvironment in regulating the functionally distinct VEGF isoforms in cancer cells.
Gail Fraizer, PhD (Advisor)
Paul Sampson, PhD (Committee Member)
Helen Piontkivska, PhD (Committee Member)
Mary Ann Raghanti, PhD (Committee Member)
53 p.

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Citations

  • Nock, S. (2015). Prostate cancer expression of vascular endothelial growth factor splice forms in hypoxia [Undergraduate thesis, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1430770359

    APA Style (7th edition)

  • Nock, Sarah. Prostate cancer expression of vascular endothelial growth factor splice forms in hypoxia. 2015. Kent State University, Undergraduate thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1430770359.

    MLA Style (8th edition)

  • Nock, Sarah. "Prostate cancer expression of vascular endothelial growth factor splice forms in hypoxia." Undergraduate thesis, Kent State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1430770359

    Chicago Manual of Style (17th edition)