Inhibiting Tumorigenesis 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 SNXl, 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 SNX I and to generate transgenic animals overexpressing SNXl in mammary glands. We have characterized a genonuc clone for SNXl and had planned to use this clone for transgenic vector construction. However, the size of the first intron in SNXl was too large for this approach to be used successfully. Instead, a WAP-SNXl cDNA vector was constructed and used to generate transgenic animals. Out of approximately 150 oocyte microinjections over a period of 6 months, only one transgene positive mouse was identified. This mouse (a female) was bred and delivered several litters but no transgenic offspring were detected A Career Development Award was a second component of the application. Career development activities include: participation as reviewer on the American Cancer Society Cell Structure and Metastasis study section, participation on a search committee charged with identifying a Director for Breast Cancer Research at UAMS and participation as a reviewer on the California Breast Cancer Research Program Pathogenesis Study Section. In addition, the State of Arkansas Breast Cancer Research Program awarded me a one-year pilot research grant to examine the relationship between HER-2/neu and EGF receptors in mammary gland cell proliferation. In Fall 2001, the UAMS Promotion and Tenure committee approved my application for promotion to Associate Professor with tenure.