Do EBV Encoded Small RNAs Interfere With Tumor Suppressor APC in EBV Associated Breast Cancers
Annual rept. 15 Jul 2004-14 Jul 2005
BOSTON UNIV MA
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Epstein Barr virus EBV infection in human is associated with variety of malignant diseases including Burkiffs Lymphoma BL nasopharyngeal carcinoma Hodgkins disease and lympho proliferative disorders of immuno suppressed patients as well as significant portion of estrogen receptor negative invasive breast cancers and large numbers of rapidly growing fibroadenomas of the breast in immuno compromised patients. In all latently infected cells EBV expresses two small non-polyadenylated RNAs EBERs.Recent studies have shown that EBERs alone provide tumorigenic potential. We have identified that EBERs which possess extensive secondary structure has strong nucleotide sequence homology to the codingexon of kinesin super family of motor proteins. Kinesin is an essential member of the multiprotein u-catenin degradation complex which includes tumor suppressor adenomatos poliposis coli APO and GSK3u.catenin an activator of Wnt signaling pathway is activated in many breast cancers. We hypothesize that EBERs down regulate KlF3 protein by RNA interference mechanism and interfere with the functionality and anti-tumor activity of APO. In this proof of principle study we will analyze if EBERs indeed alter expression of KlF3 protein via RNA interference and whether such alteration provide growth advantages in mammary epithelial cells.
- Anatomy and Physiology
- Medicine and Medical Research