Inhibiting Tumorigeneis by Growth Factor Receptor Down Regulation Using a Sorting Nexin

摘要

Excessive activation of growth factor receptors can lead to the unrestrained cellular proliferation characteristic of tumors. Our objective is to determine if SNX1, a protein involved in intracellular membrane trafficking, can be used to downregulate EGF receptors in mammary gland. Our approach is to characterize the gene for SNX1 and to generate transgenic animals overexpressing SNX1 in mammary glands. We have characterized a genomic clone for SNX1 and had planned to use this clone for transgenic vector construction. However the size of the first intron in SNX1 is too large for this approach to be used successfully. The revised plan is to construct a WAP-SNX1 cDNA vector for transgenic mouse production. A Career Development Award was a second component of the application. Career development activities include: presentation of the inaugural seminar for the Arkansas Cancer Research Center Forum, participation as reviewer on the American Cancer Society Cell Structure and Metastasis study section, and participation on a search committee charged with identifying a Director for Breast Cancer Research at UAMS. In addition, the State of Arkansas Breast Cancer Research Program awarded me a one-year pilot research grant to examine the relationship between HER-2lneu and EGF receptors in mammary gland cell proliferation.