Investigating The Effects of Silencing Epha2 In Metastatic Breast Cancer Cells

<p>EphA2, also known as ECK (epithelial cell kinase), is a transmembrane receptor tyrosine kinase that is commonly over-expressed in cancers such as those of the prostate, colon, lung, and breast. For breast cancers, EphA2 overexpression is most prominent in the ER-negative subtype, and is associated with a higher rate of lung metastasis. Studies conducted to demonstrate the role of EphA2 in a non-cancerous environment have shown that it is very important in developmental processes, but not in normal adult tissues. These results make EphA2 a prospective therapeutic target since new therapies are needed for the more aggressive ER-negative breast cancers. A panel of breast cancer cell lines was screened for expression of EphA2 by immunoblotting. Several of the overexpressing cell lines, including BT549, MDA-MB-231, and HCC 1954 were selected for experiments utilizing siRNA for transient knockdown and shRNA for stable knockdown. Targeted knockdown of EphA2 was measured using RT-PCR and immunoblotting techniques. Here, the functions of EphA2 in the process of metastasis have been elucidated using <em>in vitro </em>assays that indicate cancer cell metastatic potential and <em>in vivo</em> studies that reveal the effect of EphA2 on mammary fat pad tumor growth, vessel formation, and the effect of using EphA2-targeting siRNA on pre-established mammary fat pad tumors. A decrease in EphA2 expression both <em>in vitro </em>and <em>in vivo </em>correlated with reduced migration and experimental metastasis of breast cancer cells. Current work is being done to investigate the mechanism behind EphA2’s participation in some of these processes. These studies are important because they have contributed to understanding the role that EphA2 plays in the progression of breast cancers to a metastatic state.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2011

Author dc:creator

• Erzinger, Stephanie

Contributors dc:contributor

• Janet E. Price
• Gary Gallick
• Anil Sood

• EphA2
• Breast Cancer
• Metastatic Breast Cancer
• Metastasis
• Breast Cancer Cells
• Biology
• Cancer Biology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/116

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1142