A Genomic Approach to Identify The Notch Pathway As A Putative Tumor Suppressor In Endometrial Cancer

<p>Endometrial cancer is the most common gynecological malignancy and the fourth most frequently diagnosed cancer among women. The molecular changes that distinguish normal endometrium from endometrial carcinoma are not thoroughly understood. Identification of these changes could potentially aid in identifying at-risk women who are especially prone to develop endometrial cancer, such as obese women and women with Lynch Syndrome.</p> <p>A microarray analysis was performed using normal endometrium from thin and obese women and cancerous endometrium from obese women. We validated the differential expression of ten genes whose expression was significantly up-regulated or down-regulated using qRT-PCR. All of the genes had distinct expression levels depending on the endometrial carcinoma histotype. As a result, they could serve as molecular markers to distinguish between normal endometrium and endometrial cancer, as well as between low grade endometrial carcinomas and high grade endometrial carcinomas.</p> <p>Two of the ten genes validated, <em>HEYL</em> and <em>HES1</em>, are down-stream targets of the Notch signaling pathway. <em>HEYL</em> and <em>HES1</em> were identified by microarray and qRT-PCR to have a significant decrease in expression in endometrial carcinomas compared to normal endometrium. We further analyzed the differential expression of other components of the Notch signaling pathway, <em>Notch4</em> and <em>Jagged1</em>. They were also identified by qRT-PCR to be significantly down-regulated in endometrial carcinomas compared to normal endometrium. Therefore, we believe the Notch signaling pathway to act as a tumor suppressor in endometrial carcinomas.</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2013

Author dc:creator

• Gandhi, Rajshi

Contributors dc:contributor

• Dr. Russell R. Broaddus
• Dr. Karen H. Lu
• Dr. Rosemarie E. Schmandt

• Notch pathway
• endometrial cancer
• tumor suppressor
• Jagged1
• Notch4
• HEYL
• HES1
• gene validation
• Cancer Biology
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/394

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1429