Date of Award
Master of Science (MS)
Dr. Asma Al Menhali
To maintain cellular homeostasis, the epithelial lining of the stomach wall continuously fluctuates between cellular proliferation, differentiation, and apoptosis. A key player in this process is the gastric stem cell (GSC). GSCs are located in the isthmus region of the corpus gastric gland and have the potential to proliferate and differentiate. Although several pathways have been identified to regulate stem cell role in several body tissues, little is known about controlling GSC homeostasis. This project aims to study the role of estrogen (E2) in GSC homeostasis using the well-established mouse gastric epithelial progenitor (mGEP) cell line. Our data showed that both estrogen receptor (ER) subunits alpha and beta are expressed in the mGEP cells at mRNA and protein levels. Incubation of mGEP cells with the commonly used selective estrogen receptor modulator (SERM) -tamoxifen- (4-OHT) decreased the cellular viability in a time and concentration-dependent manner. Cell viability was not significantly changed in the E2 treated cells. By using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), ER target genes such as insulin-like growth factor 1 receptor (Igf1r), cyclin D1 (Ccnd1), low-density lipoprotein receptor (Ldlr), interleukin-6 (Il-6) and vascular endothelial growth factor A (Vegfa) generally showed a concentration-dependent decrease of expression when treated with 4-OHT confirming that 4-OHT works as an antagonist to ERα. This well-controlled in vitro system helps to understand the impact of E2 signalling on GSC homeostasis. Especially since the effect of 4-OHT on the stomach of breast cancer patients is not fully studied.
Alkaabi, Aysha Mohamed Yusuf, "THE ROLE OF ESTROGEN IN MOUSE GASTRIC STEM CELL HOMEOSTASIS" (2017). Theses. 878.