Akademik Veri Yönetim Sistemi
Tezin Türü: Yüksek Lisans
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Biyolojik Bilimler Bölümü, Türkiye
Tezin Onay Tarihi: 2017
Öğrenci: ESİN GÜLCE SEZA
Danışman: SREEPARNA BANERJEE
Özet:Aldo-keto reductases (AKRs) are nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) dependent oxidoreductases that are involved in many anabolic and catabolic reactions. When they are over-activated, the polyol pathway is activated that results in oxidative stress. AKRs are implicated in many inflammation-associated diseases including diabetes mellitus, asthma, uveitis, sepsis, atherosclerosis, periodontitis, and many cancers. AKR1B10, a member of the AKR family that is also known as small intestine like aldose reductase is highly expressed in the small intestine and colon. Analysis of publicly available microarray datasets indicated that colorectal cancer (CRC) patients showed lower AKR1B10 expression compared to normal tissues, although AKR1B10 was overexpressed in other cancers such as liver cancer. Gene set enrichment analyses indicated significant enrichment of metabolism related genes in tumors that expressed high amounts of AKR1B10. In order to understand the functional effects of AKR1B10, we overexpressed AKR1B10 in CRC cell lines that do not express the protein. We observed no alterations in cellular proliferation or cell cycle; however, cellular motility was reduced, along with a decrease in the nuclear translocation, DNA binding and transcriptional activity of NF-B, which is an important transcription factor that is necessary for cell survival and inflammation. The work carried out in this thesis suggests that the expression of AKR1B10 in colon cancer cells may not directly affect cancer progression by affecting cell proliferation or cell cycle; rather, the protein has a more indirect effect, perhaps through the activation of metabolism related pathways.